AIDSTruth.org - Features

Quackery taken to task

Eduard Grebe — Thu, 25 Mar 2010 12:53:34 +0000

by Lesley Odendal

OPINION:Nathan Geffen’s book Debunking Delusions reminds us what can go wrong when AIDS denialists are given the time of day. The book also documents clearly how we can fight denialism in a manner that saves lives and respects science. What is clear given the resurgence of AIDS denialist propaganda is that now is not the time to sit back.

As Geffen argues in his book, underlying the Treatment Action Campaign’s success in fighting denialism and quackery was the almost unsung treatment education programme. Knowledge truly is power in this case.

AIDS denialism reached its peak in the public arena in the late nineties and early 2000s when Thabo Mbeki consulted a number of AIDS denialistson his AIDS panel to advise him on AIDS policy. The public believed that the debate was over when Mbeki ‘withdrew’ from the debate, claiming that he never stated that HIV did not cause AIDS and when in 2003 antiretroviral (ARVs) began to be rolled out at a national scale to HIV-infected people. The struggle between the many players, including Mbeki, then Minister of Health Manto Tshablala-Msimang, the Treatment Action Campaign, clinicians, the international scientific community and the many denialists benefiting from, and supporting, Mbeki’s policies such as Duesberg, Anthony Brink, the Visser family and the numerous quacks in tow, received much media attention and mass mobilization.

In 2010, one may ask, what is the significance of AIDS denialism today? For most lay people, the debate is settled and the evidence is clear: HIV causes AIDS; ARVs are the best and only treatment for HIV; Mbeki’s AIDS policies caused thousands of unnecessary deaths and HIV-infections and thousands of peer-reviewed articles have been written regarding the effects of HIV on the body.

Unfortunately, the denialists are not ready to give up. Despite the numerous rebuttals against their claims and the plethora of evidence that exists against them, there has been a recent surge in denialist material that has been circulating both in the mass media in the form of the documentary House of Numbers and the infamous AIDS denialist Peter Deusberg’s (who was also on Mbeki’s panel) article in the non-peer reviewed journal Medical Hypothesis. Medical Hypothesis as not being peer reviewed and scandals around that

AIDS denialists usually support at least one of the following hypothesis:

HIV does not exist
HIV tests do not in detect the presence of HIV
Following from this, HIV prevalence is highly overestimated
HIV does exist but it is not harmless
HIV is not sexually transmitted
AIDS is caused by other factors such as poverty, malnutrition or ARVs themselves
ARVs are toxic and often fatal and cannot prevent the vertical transmission of HIV
AIDS should be treated by an extensive range of alternative remedies such as herbal concoctions, vegetables, vitamins or bizarre treatments such as ozone rectal therapy

Pride Chigwedere of the Harvard School of Public Health eloquently and passionately refutes many of these claims and the amount of words spent on deconstructing the claims of denialists is unprecedented in academia. However, what is evident and a hallmark of AIDS denialist argument is that despite any proven evidence that is thrown against them, AIDS denialists do not take this into account for developing their arguments and instead sway the debate in another direction. For them, the evidence is incorrect and they are misunderstood as the last renegades of the truth. This makes it very difficult to engage in anti-denialist debates— academics, scientists, activists and clinicians grow tired of arguing with those who do not take reason into account and who do not respect the essential tenant of science— proven evidence—and prefer to focus on their core work which is to create and disseminate more evidence to the benefit of our understanding of HIV. As Nattrass states, “the problem [of not accepting evidence] is far more than intellectual because disregarding evidence not only undermines scientific progress, but it threatens the social basis which makes such progress possible.”

More worrying, is that where the evidence suits them, AIDS denialists misrepresent data or use the incorrect data to support their arguments. In Duesberg’s article for instance, he uses the incorrect epidemiological data that misclassifies causes of death in South Africa to support his thesis that AIDS is not killing as many people as it is widely estimated by scientists across the world. Duesberg uses the Statistics South Africa Findings from Death Notification to argue that AIDS-related deaths are much lower than that postulated by Chigwedere’s 2008 article. However, it is a common fact, that due to AIDS stigma, AIDS is rarely stated as the reason for death. Up to 60% of HIV deaths are misclassified.

Duesberg also refutes the claim that ARVs are effective at preventing vertical transmission of HIV. He does not quote the numerous randomised control trials that prove that ARVs do decrease the vertical transmission down to between 3 and 5 % when properly administered, but instead examines the history of the production of AZT, one of he drugs used in this prevention strategy.

In the newly aired House of Numbers documentary, denialist views are supported by interviewing respected scientists and distorting their views in a clever concert of manipulation. The public is further shown as erratic sheep who merely carry mainstream HIV because that’s what ‘they’, the scientists said. The definition of HIV and AIDS is painted as unclear with the claim that there is confusion as to what the more than thirty-year old disease, AIDS is. The effectiveness of HIV rapid-tests are questioned in a most irresponsible manner. HIV counsellors in South Africa explain at length what the limitations of rapid testing are and why it is necessary to conduct follow-up testing. At no point is the practical or economic convenience of rapid testing explained, nor is there mention of the gold standard test PCR HIV test which instead of searching for HIV antibodies, identifies HIV DNA in the person’s blood.

The causes of AIDS are debated at length as if the evidence has not been around for decades— HIV as being caused by ‘lifestyle’ drugs and choices such as Poppers, being homosexual, or by co-factors such as poverty and malnutrition. People living with HIV are depicted as highly-emotional sufferers who do not have an option to take life-saving medication and at no point are any people who are managing their lives well on ARVs interviewed. Instead, a baby who was clearly suffering from a very common ARV side effect, plural neuropathy, is depicted as being cured of the ailment once she is off the drug. Other patients are described as having died of hepatoxicity from Nevirapine. At no point is it explained that these side effects are well known and well documented and that every countries ARV guidelines takes these into account in the prescription of ARVs.

Just as Duesberg does, House of Numbers is another example of selective use of evidence. The consequences of this kind of conspiracy theory manipulation of evidence can be far reaching as can be witnessed in South Africa’s tragic AIDS policy of the past. House of Numbers is currently being screened at film festivals around the world. Like all other AIDS denialism, there are dire consequences to this kind of portrayal of evidence.

AIDS denialism allows for deadly consequences. Firstly, it allows people living with HIV an escape— a far too easy route into personal denial that facilitates a process of withholding treatment from oneself and taking the necessary steps to ensure a healthy future. Stemming from this, AIDS denialism allows for quackery in all forms to persist. This allows for unfounded treatments to be sold to people at high costs to cure them of their HIV, as has been tragically witnessed in so many individuals across the world. This is what resulted in the deaths of an immeasurable amount of people across the world, as ARVs are distrusted, as is the institution of scientific evidence. More than quackery, there is a current wave of religious leaders who are encouraging people to stop taking their ARVs as only their faith can heal them.

AIDS denialism, when lent a powerful policy ear, as was the case with the Mbeki administration, allows for the systematic erosion of the scientific governance of medicine. This has far reaching consequences— for example the Medical Control Council (MCC) is practically defunct due to Mbeki’s consistent disregard for scientific evidence. It can result in delaying life-saving treatment to entire nations.

Most importantly, denialism results in death. Unnecessary, painful death. It can be genocide. And it is for that reason that the activists and scientists should not stop fighting AIDS denialism. This should not only be on blogs and in academic journals—most importantly, it should be in the public. HIV Treatment Literacy (TL) is our most powerful tool in this. It is about making science accessible to the masses— even those who do not have any form of education. There are numerous groups who have shown the success of this approach. At any time one can walk into any clinic in Khayelitsha and hear TAC activists, many with no formal education, educating patients about their disease and its treatment. This is the power of TL and anti-denialists strongest weapon in essence given the fact that the denialists themselves are failing to listen.

At the book launch of Debunking Denialism, Andile Madondile, a TAC TL educator, who had indulged in quack remedies for his HIV when his CD 4 was only 9, spoke honestly of the effect that treatment literacy had on him “The comrades at TAC saved my life. They made me realise that ARVs were the only way that I was going to overcome this disease. It is the reason I am alive and well today.”

The denialists appear to be making a comeback. The sad and worrying truth is that they were never gone. The issue at stake here is that due to their easy access to money, resources, publicity, journals which are not peer reviewed and internet, their message will continue to be heard by the masses, who do not necessarily have an understanding of how science works or the myriad of AIDS data. It is this which needs to be stopped in its tracks. Even if governments are clear on the causes and treatment of HIV, at an individual level there is a different story, and this is where our efforts should be targeted. Nathan Geffen’s book Debunking Delusions comes at a time when we need to fight for truth again.

Lesley Odendal is currently completing her Masters in Public Health. She worked at the Treatment Action Campaign in 2008 and 2009.

The Price of Denial: A documentary on the legacy of AIDS denialism in South Africa

Eduard Grebe — Sat, 30 Jan 2010 12:54:36 +0000

This documentary was produced by the non-profit health news agency Health-e and was recently broadcast on an independent television channel in South Africa.

View Part I:

(If you do not see the video above, your browser does not support HTML5 video playback. Download the video or visit this page in Firefox or Chrome.)
Download Part I in ogg/theora or in mp4.

Part II after the jump.

View Part II

Download Part II in ogg/theora or in mp4.

New myth debunked: The fact that some HIV-positive people live in good health without treatment for many years proves that HIV is harmless

Eduard Grebe — Mon, 11 Jan 2010 16:12:51 +0000

Fact: A small percentage of people infected with HIV do live for many years without developing AIDS. They are often known as long-term non-progressors. But such individuals are rare: without proper medical care, including antiretroviral drugs when needed, most HIV-positive people will eventually develop AIDS.

As putative evidence that HIV is harmless, some HIV/AIDS denialists point to examples of HIV-infected people who survive for many years, even decades, without receiving antiretroviral treatment. HIV denialists often claim that these people survived because they avoided antiretroviral therapy, and that diet, exercise, nutritional supplements or herbal therapies, stress reduction, hypnosis, and other interventions prevent progression to AIDS. These claims are untrue and dangerous.

Read the full bebunking.

In Memoriam, Lambros Papantoniou

Eduard Grebe — Wed, 02 Dec 2009 16:38:17 +0000

by George N. Pavlakis, Rockville, MD USA

What do you do about someone who claims to be an expert, serving up half-truths, twisting the facts in credible-sounding sentences and misleading a patient? There must be some rules that apply to someone who professes to be an expert and induces patients to stop their doctor-prescribed medication. These must be applied to prevent harm to more patients. And what if these actions lead to the patient’s death?

Such is the case of Lambros Papantoniou, a journalist living in Washington, a diplomatic correspondent for several Greek media institutions for more than 30 years and a man loved by all who met him. Even in the higher political echelons of Washington, he was affectionately known as “Mr Lambros”.

During a hospital stay approximately ten years ago, Lambros was diagnosed with AIDS and given anti-retroviral therapy. Following this, his interest in the AIDS problem skyrocketed, and he sought information on it. Although he was a diplomatic correspondent, he reported on AIDS issues several times.

Unfortunately, Lambros attracted the attention of Andrew Maniotis, a scientist and self-proclaimed expert on many fields, and AIDS denialist. Dr. Maniotis is not a medical doctor, nor a pathologist, as he occasionally describes himself. He is not a tenured professor, nor a tenure-track candidate for a higher academic career. At times he denies he is an “AIDS denialist,” but this term accurately describes public opinions. He does not shy away from controversy and publicizes naïve opinions that contradict the established knowledge and medical science, trying to nullify the medical gains of generations of researchers and doctors.

Maniotis claims that Lambros was like a brother to him. With such brothers, who needs enemies? The two men became friends, and Maniotis visited Lambros often in the last few years, his influence growing stronger and stronger, ultimately convincing him that HIV did not exist. Lambros stopped taking his medication and the result was devastating. After his death, Lambros’s family and friends found his medication in his refrigerator, untouched since 2007. Instead of his life-saving doctor prescribed medicine, Lambros was convinced to consume Maniotis-promoted vitamins.

During 2007, increasingly influenced by Maniotis, Lambros became more aggressive in interrogating scientists and government officials about AIDS. In his attempts to discredit Dr. Robert Gallo, Maniotis urged Lambros to seek an interview with Gallo, hoping to confront him with an AIDS denialist agenda and publish articles containing slander and misinformation.

Dr. Gallo took the bait and spoke with Lambros openly and frankly. To his credit, Lambros published a series of articles in which he reported on the issue ethically and to the best of his ability. Undaunted by this failure, Maniotis intensified his efforts to convince Lambros of his outlandish ideas on AIDS. Lambros was finally convinced and published an extensive interview, in which Maniotis disputes all scientific facts about HIV and AIDS, advising HIV positive people, like Lambros himself, to stop taking their doctor-prescribed medication and to rely on vitamins and other unproven methods.

Unfortunately, Lambros’ non-scientific background and his personal vulnerability as an HIV positive person got the best of him, and he became more and more a spokesperson of the AIDS denialists, putting his complete trust in Maniotis.

This trust eventually cost him his life. He simply stopped taking his medication. Already hospitalized once, Lambros’s health depended on blocking HIV through anti-retroviral drugs. Without this protection, the virus continues to damage the immune system, until the patient becomes vulnerable to a multitude of common infectious agents, which would ordinarily be blocked by a functioning immune system. With the medication, he likely would have lived a longer and healthier life.

Having finally succumbed to Maniotis’ 'freindship', at several White House and State Department briefings in Washington, Lambros asked hostile nonsensical questions repeating the statements of Maniotis verbatim. He asked whether anyone had actually seen the virus. He accused the medical profession of poisoning the “so-called AIDS” patients with drugs.

In retrospect, Lambros’ increasingly erratic behavior can be partially explained by his deteriorating health. HIV ultimately landed him at Howard University Hospital under unclear circumstances. The most likely scenario is that he was found confused and disoriented and was taken to the closest emergency room. He had developed encephalitis, a common outcome of end-stage HIV infection. He was later transferred to Georgetown Hospital, where he died of encephalitis. During his more lucid moments at the hospital, Lambros told his friends he was dying of AIDS.

In the meantime, Maniotis, having the trust of Lambros’s family, was calling both hospitals and arguing about prescribed treatments, accusing medical personnel of trying to kill Lambros, all while denying the existence of AIDS. The doctors found the situation highly distracting and asked that Maniotis does not contact them. The Greek Embassy had to intervene and tell Maniotis to back off.

During this last period of his life, Lambros was clearly very sick and confused, making several statements reflecting this confusion. To their shame, AIDS denialists are promoting these statements on the Internet in order to build up their own agenda, disrespecting the memory of a sick and confused man, and, of course, not acknowledging their part in his death.

"Nobody really knows why he's gone," claims Maniotis. But in the end, Lambros knew, and so do we. He died of encephalitis following the collapse of his immune system, an outcome of HIV infection. We know from millions of other cases that, had he taken his anti-retroviral medicine and prevented further damage by HIV, he could have had many more productive years.

Some of us who knew him also feel a bit guilty at times about not being able to protect him more from predators like Maniotis.

Consequently, we feel that along with celebrating his contributions, his achievements, his life of giving, of helping many people in his community, we also need to tell his true story. Lambros was a defender of our democratic ideals, a stalwart defender of the truth, a man who gave freely of himself, his time and the limited money he had, helping countless people in his neighborhood in Washington, in cities throughout the U.S. and in Greece. He is missed even by those he criticized.

We must honor him by not allowing his death to be used to hurt others. We must not be silent, as silence did not become Lambros himself.

As a generation of AIDS activists realized some time ago, Silence = Death.

Rian Malan still getting AIDS stats wrong

Eduard Grebe — Tue, 01 Dec 2009 13:09:43 +0000

by Nathan Geffen, 1 December 2009

Substantially updated by the author on 7 December 2009

In a piece published in Rapport newspaper and on politicsweb, Rian Malan claims:

[D]on't trust anything the Aids bwanas say - especially not Nathan Geffen of TAC. Earlier this week, he informed the world that Zuma's mistake "was of little consequence," because other data showed that SA's death rate has doubled since l997. Hmmm. It is true that annual death registrations rose from 316,000 in 1997 to around 600,000 in 2007, but it is absurd to claim, as Geffen did, that this was almost entirely the result of Aids.

Over the same period, completeness of registration rose from around 67 percent to 81 percent, according to Stats SA, while our population rose by close on seven million. If you adjust the raw numbers accordingly, Geffen's apparent doubling shrinks to an increase of around 15 to 20 percent.

He then published a correction:

Correction: I am informed that my mathematical skills leave much to be desired. If you run the numbers in the penultimate paragraph correctly, the real increase in SA death registrations since l997 comes out at around 30 percent - still a tragedy by any reckoning, but still way short of the doubling claimed by Geffen.

First let's deal with the numbers. Malan continues to get it wrong, even in his correction. AIDS deaths have conservatively increased 6-fold since 1997, from approximately 50,000 to well over 300,000 in 2006 as well as 2007 and maybe even over 350,000, meaning the real increase in deaths -which is way more than 30%- recorded or otherwise, was mainly due to AIDS. The ASSA2003 interventions model calculates under 150,000 AIDS deaths in 2000 and about 360,000 in 2007. Approximately 45% of deaths in 2006 and 2007 were due to AIDS. The model probably overestimates AIDS deaths but not substantially enough to give any material support to Malan's argument. But even a 30% increase in mortality, as Malan acknowledges, is a tragedy.

Far more knowledgeable people than either Malan or myself work on the ASSA model. They take into account all the available data: recorded deaths, improved registration, population growth and much else. Of course, as with any model, there is a good deal of uncertainty, but it is the best we have to go on - and far better than Malan, who admits his mathematical skills leave much to be desired.

In Malan's Rolling Stone article in 2001, his arguments were based on outright AIDS denialism, in which he confused the different types of testing algorithms needed for diagnosis of an individual patient versus epidemiological surveys. His articles in 2003 in Spectator and Noseweek continued in the same vein. But with each subsequent article he has come closer and closer to admitting the massive scale of the HIV epidemic. His latest acknowledgement that AIDS is responsible for a 30% increase in mortality is almost mainstream. Yet his writing style remains unrepentant and he brushes off as a triviality the realisation that he is not mathematically competent to do this work.

He also misrepresents me. Nowhere did I write that real deaths had doubled in my recent article that he appears to be referring to. I wrote, accurately, that recorded deaths increased over 90% in a decade. I also wrote, "Improved death registration and population growth can account for only a small portion of this increase. The vast majority of additional deaths are due to the HIV epidemic."

This was also accurate. Only a careless reading of my wording would imply that total deaths (i.e. recorded plus unrecorded) have doubled due to AIDS. This might seem a minor "He said, I said" spat, but it demonstrates a lack of integrity in public engagement. Despite our overall success, I am sure there is much fair criticism that can be directed at TAC about our actions over the last decade, but manipulating AIDS statistics is not one of them.

Without any sense of irony, Malan concludes, "we should just ignore those who try to manipulate us with numbers and support Zuma's common-sense plan to stamp out the disease." Actually, it is because of the people who Malan falsely accuses of manipulation that we finally have a common-sense AIDS plan. While we were fighting for it, Malan was supporting Mbeki on AIDS.

Some of my colleagues have been weary about me responding to Malan. They have warned me that he is being a contrarian so that he can promote his new book and that a response is exactly what he wants. But I think Malan is a talented wordsmith whose writing style convinces some people; it is them I aim my articles at. But being clever with words does not imply competence and Malan's articles on AIDS are littered with errors.

According to Wikipedia Malan stated, "I get a kick out of it when the Treatment Action Campaign attacks me; it's like sport." I do not know if he really said this, but it does appear to be sport for him.

For TAC and me, it is a waste of precious time and aggravating. Many people find AIDS statistics impersonal. But I do not; they remind me of Christopher Moraka, who testified before Parliament in 2000 that he could not get medicines to treat his systemic thrush. He died a couple of months later. Or Edward Mabunda, TAC's late firebrand poet. And Ronald Louw, a close friend and brilliant lawyer based at UKZN who died a few years ago of AIDS. No, this debate is not sport for TAC or me.

Constantine and Weiss pinpoint misrepresentations

Eduard Grebe — Thu, 26 Nov 2009 20:22:29 +0000

Statements by Professor Niel Constantine and Professor Robin Weiss about the Misrepresentation of their Interviews in “House of Numbers.”

Posted November 23, 2009, to HouseofNumbers.org

The sections on HIV antibody tests in “House of Numbers” contain fragments of interviews with a number of different people, put together in a way that confuses viewers rather than clarifying what HIV testing protocols are and how they work. The editing of the interviews to try to create doubts about the worth of HIV diagnostic assays is surely intentional. Questioning HIV diagnostics is one of the main tactics of HIV denialism.

The talking heads in these sections of the video include an eager-to-please but inexpert woman working in a temporary testing tent in a South African mall, several legitimate scientists, and HIV denialist Liam Scheff and filmmaker Brent Leung. The section jumbles together bits of speech about the use of HIV antibody testing for different purposes—for screening the blood supply, for screening individuals for HIV infection and confirmatory testing, for diagnosis and for prognosis. It also scrambles remarks about different generations of tests; about tests of different qualities—those manufactured under FDA oversight and those produced in uncontrolled conditions; about different types of HIV antibody tests—conventional and rapid tests, ELISA and Western Blot; and about the use of these tests under different countries’ government protocols—Germany, South Africa, Britain, the USA. The resulting mess of words creates confusion – as it was intended to.

The history, variety, and protocols of HIV antibody testing can be confusing to non-experts. Leung and his team have exploited this in the film. But any of the legitimate scientists or clinicians in the film, asked a clear question by an ethical interviewer who would try to present their views accurately, could easily explain how HIV antibody testing works, what protocols are used to maximize accuracy in different places and at different times, the distinctions between screening and diagnostic assays, the differences between ELISAs and Western Blots, and so on. But Brent Leung sought to confuse, not clarify. He wanted to make it seem like the tests are unreliable and that the scientists he interviewed didn’t know disagreed with each other about HIV tests. The reality is very different. HIV antibody tests are extremely accurate, and various confirming protocols (two or three different types of tests) are used in different places.

Two scientists who were interviewed by Leung, then edited to appear as if they held antagonistic views, are Niel Constantine, Professor of Pathology at the University of Maryland, and Robin Weiss, Professor of Viral Oncology in the Division of Infection and Immunity at University College, London. Professors Constantine and Weiss both say that their interview footage as edited misrepresented what they know and what they said. In fact, contrary to the impression created in “House of Numbers”, they agree with one another about the nature, value, and accuracy of HIV antibody tests. Here are their statements.

Dr. Constantine's Statement

“What Mr. Leung has done is take our statements completely out of context. For example, he and I were discussing the use of rapid HIV tests and their accuracy. I explained that the tests were excellent, but that some individuals were assembling rapid HIV tests from individually purchased components and making these tests in their garages for sale. Such tests, that had not been subjected to the quality assurance measures required by organizations such as the FDA, were inferior and should not be used. That is, only tests that were approved by expert organizations should be used. Hence, my statement in the film "Now if I tell you that the test you took was lousy and didn't mean a thing." Mr. Leung used this to imply that I was stating that HIV tests were useless.”

-- Niel T. Constantine, Ph.D., Professor of Pathology, University of Maryland School of Medicine

Dr. Weiss's Statement

“The sound bites were extracted out of quite a long interview with me and presented out of context. In my recollection (I don't have a tape of the interview) Leung was pressing me about HIV antibody tests in reference to screening blood donations. When I said ‘I don't think the Western Blot is a useful diagnostic test; I don't think it's worth doing’, I was referring to relatively high throughput screening for blood banks, and in the mid 1980s we did not yet have commercial dip stick Western Blot kits available. In retrospect, it would have been better for me to say: ‘I don't think the Western Blot was a useful primary screening test’.

“I also cited what I regarded as a dogma that a Western Blot test was essential as a confirmatory test; ELISA tests made by two different manufacturers can also provide a confirmed result. For instance, in some UK labs the Wellcozyme ELISA using a competition format was used for primary screening and was then followed up with a confirmatory assay using the Abbott standard direct-binding ELISA instead of a Western Blot.

“It strikes me that similar false contrast and out of context quotes have been crafted together throughout the programme. Furthermore, Leung doesn't seem to understand or acknowledge that doubts about the precision or reliability of tests that were devised as research tools in 1984 (the first year in which we could grow HIV in reasonable amounts in the lab) really have little relevance to the reliability of subsequent mass produced commercial tests, which had to go through extensive quality control before they were marketed or used in clinics and blood banks. It's rather like saying that Roentgen's original fuzzy X-ray pictures are a valid reason for debunking today's radiological imaging systems for hospital diagnosis.”

-- Robin A Weiss, Ph.D., Professor of Viral Oncology, Division of Infection and Immunity, University College London

The following text is an annotated transcript of the sections of the video about HIV antibody testing, to provide a context for Professor Constantine’s and Professor Weiss’ statements. Annotations in italics.

Scene: Brent Leung is getting an HIV test in a South African mall.

African woman tester: “We always say to our clients: even if you have tested here, you can go to other centers and go and verify your test. We cannot say you’re 100%. Because you find clients going from area to area doing these tests, and they come with stories that I was negative at a certain area and positive with you.” She seems to be talking about people who are HIV+ testing repeatedly at different sites in hopes of getting negative results.

Leung: “And how do they decide if they are positive or negative?”

Tester: “We cannot tell, because we are using a rapid test.” This answer doesn’t mean the rapid test is useless, but that it requires confirmation.

Audio: Sinister background music.

Leung, narrating to impose a particular interpretation on the interview snippets: “It occurred to me that perhaps the HIV epidemic is reported to be so widespread in South Africa and other poor nations simply because they use these inaccurate tests.”

Image: flooded African shantytown.

James Chin, MD, MPH- Chief of Global HIV Surveillance World Health Organization 1987-92: “There’s the saying that if you knew how sausages, what sausages are made of, most people would hesitate to sort of eat them because they wouldn’t like what’s in it; and if you knew how HIV numbers are cooked, uh.. or made up, you would use them with extreme caution.”

This is a completely different topic—how HIV statistics are estimated—but the insertion of this sentence here makes it seem that Chin is discussing HIV tests.

Caption: London, England. View of London, Thames from above.

Leung: “I decided to investigate HIV testing protocols used throughout the developed world.”

Harold Jaffe MD, Director, CDC AIDS Division 1992-95 Head of Public Health Dept. Oxford 2004- Present: “When we are testing people for HIV, the first thing we do is a screening test and it’s usually a test called the “ELISA” Jaffe’s sentence is cut off here.

Niel T. Constantine PhD- Director, Clinical Immunology Institute of Human Virology: “But there are also now available rapid assays that can be used as screening methods.”

Liam Scheff, HIV denialist: “Because they’re faster, and we all know, faster and cheaper is more efficient.”

And people don’t need to wait two weeks for highly accurate results. Is this bad?

Claudia Kücherer, MD, Molecular Biologist, Robert Koch Institute, Germany: “If an ELISA is positive, it does not mean that the patient is HIV positive. So that’s a problem.” But what did she then go on to say as an explanation of this statement? We are not shown, as Leung only manipulates sound bites.

Robin Weiss PhD- Professor of Viral Oncology University College London: “If we’re using antibodies as a screening test to tell who is infected or not, uh, very occasionally you can get false positives.”

Niel T. Constantine: “So screening tests by themselves should not be used as a definitive measure of infection; that’s why we use a screening test to pick up all the cases, but we use a confirmatory test to eliminate any false positives.

Back to the South African testing booth:

Tester: “Take it easy… I’ll pierce at the site.” She pricks Leung’s finger.

*Leung [voice over]: “It should be emphasized that most of the developing world uses only screening tests to confirm an HIV diagnosis; there are not confirmatory tests.” Leung is presumably referring to the use a second ELISA test from a different manufacturer, in contrast to a Western Blot, for confirmation. This is a highly accurate protocol and necessary where resources are limited.

Robert C. Gallo: “This has a margin of error done properly that’s extremely low. In other words, it’s one of medicine’s better tests.”

Robin Weiss: “I don’t think the Western Blot is a useful diagnostic test; I don’t think it’s worth doing.” See Dr. Weiss’s explanation of this sentence.

Niel T. Constantine: “Did he give a reason? You know anybody can say anything, I think it’s stupid to drive a car. But come on you gotta give a reason!”

In the background, Leung starts to say, “He said…”

Robin Weiss: “It’s a useful prognostic test. Once you know that someone is infected, then you can follow their antibody responses well with Western Blots.” This is a true, accurate statement.

Niel T. Constantine: “I’d say he’s absolutely wrong, it has a complete usefulness.” With what statement is Professor Constantine disagreeing here? The film doesn’t show

Footage pans backs and forth between the two men in a blurred, swinging motion, juxtaposing them to impose a sense of concurrency and argument.

Robin Weiss: “You don’t need a Western Blot! And it’s become a dogma in HIV research that you need one ELISA followed by a western; you don’t. You need two different kinds of ELISAs made in two different formats.” Professor Weiss here emphasizes the need for using two independent tests to obtain confirmation of HIV status. Most countries still use an ELISA followed by a Western Blot, a long established and highly reliable procedure. Professor Weiss simply says that there is an alternative method that could now be used and expresses his opinion that using two ELISAs is the better option.

Leung: “Would you ever want to confirm somebody is positive using just ELISAs? “

Claudia Koshered: “No. Never. It’s not…It’s against the rules, it’s against the recommendations.” In Germany, that is true, but not everywhere. Different nations make different decisions on many aspects of health care all the time.

Liam Scheff: “It’s a turbulent sea of argument about how can we use this test, when can we use this test, why does this test have no standard?” Tests made by different manufacturers are slightly different, and are read differently. However, all approved tests are very accurate. It is a profound logical error to say that if screening or measuring tests vary, the thing they screen for or measure does not exist

Niel T. Constantine: “Now if I tell you that the test you took was lousy and didn’t mean a thing, would that make any difference for everybody to hear?” See Dr. Constantine’s statement about the proper context for this comment: he is referring to bootleg tests that are not reliable.

Leung: “It’ll make a difference for me.”

Niel T. Constantine: “Yeah I know.”

Science, pseudoscience and professional responsibility

Eduard Grebe — Thu, 26 Nov 2009 15:05:04 +0000

by Dr John Moore, PhD (Originally published by health-e)

Surveys have consistently shown that over 40% of Americans do not believe in evolution. It is not surprising, then, that our society is vulnerable to being fooled by people who misrepresent scientific or historical facts.

We are now all too familiar with the crazed activities of the 'Birthers', an ad hoc, right wing political group refusing to accept President Obama was born in the United States. Earlier this year, we saw media coverage of the insane views of a clique that refuses to accept American astronauts walked on the moon 40 years ago. The "9/11 Truth Movement" flourishes on the internet, arguing that the World Trade Center and the Pentagon were not hit by hijacked jetliners, but were blown up by the CIA at the behest of Israeli intelligence. Conspiracy groups like these usually do little real damage to society, although the activities of the "9/11 Truth Movement" foster anti-Semitism and insult the memories of the nearly 3000 Americans who died on 9/11. Unfortunately, other equally bizarre and factually unfounded, internet-based conspiracy groups can, and do, harm, even kill, significant numbers of people. This is not just an American problem, as the ripple effects of conspiracy theories spread worldwide via the internet. Indeed, the most serious consequences of one such group’s actions have been felt in Africa.

A small group of misguided and, in some cases malicious, individuals have long promoted the view that HIV does not cause AIDS or, in an even more bizarre twist of the truth, that HIV does not even exist. An even nastier variation of the theme is that HIV was created by the US government as a device to kill "undesirables", such as people with black skins or who are gay. None of these opinions is true, and there is not a shred of credible scientific or historic evidence to support them. Unfortunately, the Mbeki administration in South Africa put in place policies based around the premises that HIV is harmless but anti-retroviral drugs are dangerous. This decision caused over 330,000 unnecessary deaths during the first half of this decade. And yet the "AIDS Denialists" even question this death toll, a tactic no different from Holocaust Deniers asking "Did six million really die". Many Americans and Europeans have also died, persuaded by the "AIDS Denialists" that they did not need to take anti-retroviral drugs to treat their HIV infections. Distrust of the federal government and the medical establishment among African American communities has adversely affected AIDS prevention and treatment programs in the USA, in no small measure due to the crazy belief that HIV was created as a weapon of selective genocide. Indeed, this particular rumor even re-surfaced in the last Presidential election campaign. Real people die real deaths as a direct result of the pseudo-science promoted by the "AIDS Denialists".

In a similar vein, groups that claim vaccination is harmful have harmed global immunization programs, and thereby caused avoidable deaths worldwide. A conspiracy theory group often called "The Mercuries" has been particularly vociferous in its argument that a mercury-containing preservative found in some vaccines causes autism. There is less mercury in a vaccine shot than in a tuna fish sandwich, and the mercury present in the fish is in a more dangerous chemical form. Overall, a now vast body of solid scientific evidence has proven that autism has no connection whatsoever to any vaccine or vaccine component. This is now settled science within the professional community, which understands that the cause of autism is based in human genetics. But despite the facts, the distrust of vaccines that has been created by “The Mercuries” and other anti-vaccine conspiracy groups is now damaging efforts to counter swine flu by vaccination, both in America and, increasingly, elsewhere. The polio vaccine eradication campaign has been harmed, notably in Nigeria, by rumors that the vaccine is contaminated with dangerous chemicals, or even with HIV, or that it was designed by “white people to sterilize black people”. As a result, this dangerous infection has still not been eradicated from Africa, where it lingers on, killing and paralyzing yet more people.

The mindsets of the "AIDS Denialists" and "The Mercuries" are similar to each other. Both groups are irrational on the science, twisting the facts to a perverse extent and stubbornly ignoring and rejecting all the evidence that speaks against their views. Each group is bolstered by a very small number of scientists whose paper qualifications provide them with a superficial, wafer-thin veneer of academic credibility. The two conspiracy groups contain individuals who will resort to threats of violence and who harass those who dare to speak up against them. A common tactic of both groups is to smear scientists and physicians who recommend AIDS drugs or the use of vaccines as being nothing more than paid tools of the pharmaceutical industry. Yet both the "AIDS Denialists" and "The Mercuries" are supported by promoters of “alternative (i.e., quack) therapies" who have a financial interest in damning approved anti-HIV drugs or licensed vaccines. “Ambulance-chasing” lawyers have also been heavily involved with the anti-vaccine groups, fostering the hopes of grieving parents that they (and the lawyers) might receive a payout from a scientifically ill-informed jury.

The conspiracy theory groups also receive the support of a small, but noisy, subset of media professionals who seem attracted to the personalities involved, smelling stories in the controversies. This has been particularly problematic recently in the anti-vaccine arena, where some American chat shows and right wing news programs have given undue attention to “The Mercuries”. Bizarre as it may seem, the views of medically unqualified Hollywood celebrities are given equal, or even greater, weight on these shows than those of expert physicians and scientists. Science and pseudoscience should never be “balanced” in this way. To make an analogy: if a film star claimed that we should not fly on a jetliner because mercury contamination could make the wings fall off, we would simply laugh, preferring to listen to the views of qualified aeronautical engineers and metallurgists (and to our own experience as travelers). Yet, nowadays, film stars’ views on vaccine composition are given huge weight by some chat show hosts.

The "AIDS Denialists" and "The Mercuries" are no different from the "Birthers", the moon-landing hoaxers, the "9/11 Truth" members and the Holocaust Deniers in the irrationality of their views and their belief in government conspiracies and cover-ups. Indeed, some members of the various groups flit from one conspiracy-themed web site to another, seeking and finding solace in a variant form of irrationality. One of the very few academic supporters of the" AIDS Denialism" movement also investigates the Loch Ness Monster, Alien Crop Circles and other such fringe or paranormal themes. It would be funny if it were not so tragic.

What can be done about dispelling this kind of damaging nonsense? America has a strong tradition of free speech, so dangerous views will continue to be promoted, however harmful they are to public health and the best interests of society. The internet is the territory of the conspiracist, and it is likely to remain so. But media professionals should not be so unquestioning of the science when they provide airtime or column inches to those with fringe views. Controversy may help sell advertising, but at what cost?

A particular concern is that the ideas that HIV is harmless and that vaccines cause autism have been underpinned by a very few academics or physicians working in American or European universities or hospitals. These “thought leaders” for the conspiracy groups should now be made to face the professional consequences of their scientifically unsupportable actions. Is academic freedom such a precious concept that scientists can hide behind it while betraying the public so blatantly? When the facts are so solidly against views that kill people, there must be a price to pay. Post-tenure review of the progress of academic careers is something the university system could put in place if it chose to. How can bona fide universities justify their employees teaching students, even medical students, that HIV is harmless? How can academic and medical institutions still employ people whose views lead to the deaths of over 330,000 South Africans? Shielding the proponents of pseudoscience by doing nothing is a dereliction of a duty to the public. It is also moral cowardice. It is now time for Africa to speak out and demand action against those who have been responsible for so many deaths on this continent.

The Shameless Rian Malan

Eduard Grebe — Thu, 19 Nov 2009 14:17:00 +0000

by Nathan Geffen, 19 November 2009

In 2001, Rian Malan wrote an article in Rolling Stone questioning the accuracy of HIV tests in order to disparage the evidence of a growing HIV epidemic in South Africa. In 2003 he published similar articles in the Spectator and Noseweek. All these articles were replete with errors. I subsequently debunked the latter two in a January 2004 article.

One of Malan's errors was particularly serious. He presented miscalculated, massively understated estimates of AIDS deaths which he falsely attributed to Stats South Africa. As I wrote then, the mistake was so serious and obvious that it raised questions about Malan's basic competence as a research journalist -or more disturbingly- about his motives and integrity.

In Mbeki's 2004 State of the Nation speech he quoted from Malan and spoke warmly about him. It was not explicitly about HIV, but to anyone following the debate at the time, it was clear that Mbeki was grateful for Malan's support on AIDS.

In the last year and especially the last few weeks, following the speeches of President Jacob Zuma and Minister of Health Aaron Motsoaledi, state-supported AIDS denialism has been destroyed. If Malan had any shame, he would have stayed out of the public light after supporting an ideology responsible for the deaths of hundreds of thousands of people. But he is shameless and his denialist scribblings have continued (see this rebuttal of Malan by Eduard Grebe in 2007).

His latest appeared on Politicsweb on Friday 13 November. Malan pointed out, correctly, that Zuma and Motsoaledi quoted a wrong and over-stated estimate for the 2008 deaths. The mistake, based on Home Affairs data, was an honest one. In contrast to the untruths in Malan's articles, it was not in service of a deadly ideology. On the contrary, Zuma's speech and Motsoaledi's dense-with-statistics 47-slide presentation, were for the most part superb and demonstrated renewed political will to combat the epidemic.

Yet Malan wrote this jaundiced rant, “This country is full of HIV consultants and researchers and specialist HIV hacks who are paid a lots of money on account of their supposed expertise. The state president says that the Aids equivalent of an atom bomb has detonated among our people AND THERE'S NO REACTION AT ALL FROM ANY OF THEM. They all knew, like I did, that Zuma's number was bullshit, but they were perfectly happy to let it stand, cos big Aids numbers are good for business, innit? NOT ONE OF THOSE MOTHERS SAID ANYTHING! They think you are stupid and want to keep you that way.”

He also confirmed his AIDS denialism, “In other words, there is no apocalypse. No massive Aids related death surge. If anything, death registrations are stable.”

Actually, as I explained in an article on Politicsweb, there has undoubtedly been a massive AIDS-related death surge; we have simply reached the crest of that surge thanks to the ARV programme. And if the programme falters AIDS deaths will grow again. Only a shameless denialist like Malan could tell such an obvious lie – again. He is also guilty of exactly what he accuses others of: distortion of statistics to promote his career. If there is to be a commission of inquiry into AIDS denialism, Malan should be questioned about his motives and actions.

AIDS and mortality in South Africa

AIDSTruth — Wed, 18 Nov 2009 08:59:17 +0000

By Nathan Geffen, 16 November 2009

On 2 November 2009, Statistics South Africa released the latest mortality data, which goes up to 2007 (Stats SA, 2009). This table gives the number of recorded deaths per year:

Year	Number of recorded deaths by Stats SA
1997	317,131
1998	365,852
1999	381,820
2000	415,983
2001	454,847
2002	502,031
2003	556,769
2004	576,700
2005	598,054
2006	612,462
2007	601,033

You do not need to be a statistician to be astounded by this. Recorded deaths have increased over 90% in a decade. Improved death registration and population growth can account for only a small portion of this increase. The vast majority of additional deaths are due to the HIV epidemic. A huge body of evidence shows this. For example, there has been a three-fold increase in TB deaths over the same period and TB is the leading cause of death in people with HIV. Also the age pattern of the deaths --younger instead of older adults comprise the bulk of them-- and the drop in the median age of death from 51 in 1997 to 44 in 2007 are consistent with the way AIDS works. (For more detailed evidence see Dorrington et al. 2006, Dorrington et al. 2001 and Stats SA, 2002).

Also noticeable is that the number of deaths appears to have stabilised from 2005 to 2007 and perhaps has even begun to decrease slightly. This is most likely due to the state's antiretroviral (ARV) treatment programme.
Unfortunately because the public sector programme has not been well monitored and there are numerous treatment providers in the private sector, there is not accurate data on the number of people on treatment. But by using several sources of data, including figures published by the Department of Health, medical aid data and public sector ARV procurement data it is possible to make reasonable estimates. Muhammad Aarif Adam of Sanlam and Leigh Johnson of the Centre for Actuarial Research have made plausible calculations of the number of people on treatment in the middle of each year up until mid-2008, shown in the next table (Adam and Johnson, 2009).

Year	No people on treatment
2001	6,000
2002	15,000
2003	26,000
2004	47,000
2005	109000
2006	229,000
2007	371,000
2008	568,000

The programme began in earnest in 2004 and the stabilisation of the death rate has coincided with it. If you consider that many, perhaps most, of the people on the programme would be dead by now that would easily account for stemming rising deaths. Make no mistake; there has been a massive surge in deaths in South Africa for more than a decade and AIDS deaths continue to be very high; deaths might have stabilised but at a very high number. Life-expectancy declined to the low-50s. At least though, we are implementing the most effective known scientific medical intervention to mitigate the effects of the disease and it now appears that life-expectancy is increasing again.

But many unnecessary deaths occurred because of the delayed rollout of the ARV treatment programme. Two studies have conservatively estimated that former President Thabo Mbeki's AIDS denialist policies cost well over 300,000 lives (Nattrass, 2008; Chigwedere, 2008). Mbeki did not pursue this deadly policy without help though. Officials in government, civil servants and even some journalists supported his policy, tried to give it legitimacy and for a time succeeded in quashing the demand for a treatment rollout from health workers and AIDS activist organisations, like the Treatment Action Campaign (TAC). Thankfully, we have moved beyond this awful era of South African history.

PS: The last two weeks have seen what I believe is the final death-knell of state-supported AIDS denialism. Both President Zuma and Minister of Health Motsoaledi have delivered important speeches showing their intention to fight the epidemic. On page 35 of his presentation Motsoaledi quoted mortality data for 2008 from Home Affairs which appears to be far too large. I am unaware of how this number was derived and it appears to be an error. In other respects Motsoaledi's speech was excellent and his mistake is of no great importance.

References

Adam M and Johnson L. 2009. Estimation of adult antiretroviral treatment coverage in South Africa. September 2009, Vol. 99, No. 9 SAMJ

Chigwedere P. 2008. Estimating the Lost Benefits of Antiretroviral Drug Use in South Africa. JAIDS Journal of Acquired Immune Deficiency Syndromes. 49(4):410-415, December 1, 2008.

Dorrington R et al. 2001. The impact of HIV/AIDS on adult mortality in South Africa.

Dorrington R et al. 2006. The Demographic Impact of HIV/AIDS in South Africa.

Nattrass N. 2008. AIDS and the Scientific Governance of Medicine in Post-Apartheid South Africa. African Affairs 2008 107(427):157-176.

Statistics South Africa. 2002. Causes of death in South Africa 1997-2001 : Advance release of recorded causes of death.

Statistics South Africa. 2009. Mortality and causes of death in South Africa, 2007: Findings from death notification.

How to spot an AIDS denialist

Eduard Grebe — Fri, 13 Nov 2009 13:00:00 +0000

by Seth Kalichman (Originally published in the New Humanist)

Imagine that you or someone you love just received an HIV positive test result. The news is devastating. After a short time you begin to face the diagnosis. You turn to the Internet for answers. Searching the words “AIDS diagnosis” brings up thousands of websites. A whirlwind of information spins your mind. One credible-looking website, Aids.org, reads: “There is no cure for AIDS. There are drugs that can slow down the HIV virus and slow down the damage to your immune system. There is no way to ‘clear’ HIV from the body. Other drugs can prevent or treat opportunistic infections (OIs). In most cases, these drugs work very well. The newer, stronger ARVs have also helped reduce the rates of most OIs. A few OIs, however, are still very difficult to treat.”

With a click of the mouse, an equally credible-looking site, Aliveandwell.org, asks: “Did you know … Many experts contend that AIDS is not a fatal, incurable condition caused by HIV? That most of the AIDS information we receive is based on unsubstantiated assumptions, unfounded estimates and improbable predictions? That the symptoms associated with AIDS are treatable using non-toxic, immune-enhancing therapies that have restored the health of people diagnosed with AIDS and that have enabled those truly at risk to remain well?”

Which do you trust? Which do you believe? Which would you want to believe? Would you choose to believe there may be hope offered by medical treatments or would you prefer to believe that HIV is harmless? This simple example illustrates the lure of AIDS denialism.

AIDS denialism tells us what anyone would want to hear – that HIV does not cause AIDS and that if you live a “healthy lifestyle” (whatever that is) you won’t get AIDS. None of which is true. In fact, there are an estimated 33 million people in the world living with HIV infection. In 2007 there were nearly three million new HIV infections and two million people died of AIDS. People are living longer and healthier lives with HIV infection as a result of earlier detection through HIV antibody testing and the remarkable success of HIV treatments. Indeed, countries that launched aggressive testing and treatment programs, such as Brazil and Botswana, have reduced suffering and prolonged life. In contrast, South Africa delayed testing and treatment programs as a result of former President Thabo Mbeki’s AIDS denialism, policies that resulted in over 300,000 unnecessary deaths and over 35,000 infants senselessly infected with HIV. There is no rational basis for disputing these established facts, and yet rejecting the reality of AIDS is the mission of AIDS denialists.

AIDS denialism is one of several incarnations of denialism. All denialism is defined by rhetorical tactics designed to give the impression of a legitimate debate among experts when in fact there is none. Holocaust deniers claim that historians disagree about the evidence for Nazi mass gassings and systematic murder of Jews. Global warming denialists say that climatologists are torn by the evidence about climate change. 9/11 “Truth Seekers”, as clever a piece of branding as “pro-life”, say the collapse of the Twin Towers resulted from controlled demolition. Vaccine hysterics tell us that the science is split on whether vaccinations cause autism. And AIDS denialists say that scientists are in disagreement about whether HIV causes AIDS.

It is easy to be fooled by AIDS denialists. Not only do they tell us what we want to hear, they use methods of persuasion to create the illusion of debate. Just as HIV attacks our immune defences that would otherwise destroy it, AIDS denialists appeal to our sense of scepticism. Indeed, AIDS denialists refer to themselves as dissident scientists and sceptics. Denialists misuse science and rely on pseudoscience to call established fact into question. Denialists also exploit what is not known about how HIV causes AIDS to suggest that HIV may not cause AIDS at all. The more sophisticated efforts of AIDS denialism, like the “documentary” House of Numbers, are most disturbing because they use every trick in the denialist playbook to juxtapose pseudoscience with established science. The best way to recognise AIDS denialism is to know their common tricks of persuasion.

There are two sides to every debate. But just asserting there is a debate does not mean there is one. AIDS denialists rely on a small band of fake experts, mostly retired academics who proclaim that HIV does not cause AIDS. There is not a single instance of an “expert” offered by AIDS denialism that has ever actually done research on AIDS. In rare examples, denialist experts have a history of credible science only to have later gone off the deep end. The most credentialled AIDS denialists are Nobel Laureate Kari Mullis, who developed the PCR technology for sequencing the genetic code, and Peter Duesberg, Professor of Biochemistry and Molecular Biology at the University of California-Berkeley and member of the National Academy of Science. Although credentialled, neither is credible. Aside from saying HIV cannot cause AIDS, though he has done no research on AIDS, Mullis has shared his experiences on LSD and encounters with an alien fluorescent raccoon, and Duesberg, who did important work on cancer in his early career, now claims that there is no genetic basis for any cancer. Both have demonstrated an outright disregard for scientific evidence.

But beyond these two high-profile mavericks most of the “experts” in AIDS denialism are out-and-out pseudoscientists. My favourite is Henry Bauer, Emeritus Professor of Chemistry and Science Studies at Virginia Tech University, who claims to have proven that HIV cannot cause AIDS. Professor Bauer is also a self-proclaimed international expert on the existence of the Loch Ness Monster. Detecting fake experts requires looking beyond college degrees and achievements from decades gone by. Do not confuse credentials with credibility. Saying that there is no genetic basis for any cancer, describing extraterrestrial experiences, and searching for big green monsters in Scottish waters should matter when examining the credibility of someone making important claims about the causes of a devastating disease.

In the 1980s legitimate scientists disagreed about AIDS. For AIDS deniers, everything old is new again. AIDS denialists rely on selected research findings from the days when not much was known about AIDS. The first tests for HIV antibodies were less reliable than current testing technologies. There were early debates about what caused AIDS and good ideas that turned out to be dead ends. The drug AZT was prescribed in massive and often toxic doses. But none of this is true any more. Though there remain many debates in medical science about how HIV causes AIDS, there is no longer a debate about whether HIV causes AIDS. Unfortunately, outdated scientific literature is not purged when new knowledge emerges. AIDS deniers use this information to create the illusion of a live debate. Denialists select old findings that support their flawed logic because they have no evidence of their own. Cherrypicking is another favourite rhetorical technique of denialists. This involves selecting a lone scientific finding, presenting the results out of context, and deploying it as evidence for their own conclusions.

Another popular denialist manoeuvre is to call for a definitive single study, analogous to the creationist demand for a definitive transitional fossil to prove evolution. Peter Duesberg for example, asserts that “There is not a single controlled epidemiological study to confirm the postulated viral etiology of AIDS.” He is right about this. No one scientific study ever “proves” anything. Scientists are cautious to draw conclusions from even a series of experiments. To establish that HIV causes AIDS required countless laboratory, clinical, and epidemiological studies, all converging to a definitive conclusion. There is no single scientific paper proving that HIV causes AIDS, just as there is also no single physics experiment proving that a man could land on the moon, no single study that proves excessive exposure to the sun causes skin cancer or one study that proves smoking causes lung cancer. Rather there are tens of thousands of studies containing a wide range of evidence that, taken together, make an overwhelming case.

AIDS denialists will also demand even more specific evidence, only to change the demand once the evidence is produced. One example of this “pushing back the goalpost” technique was the former Sunday Times journalist and prominent AIDS denier Neville Hodgkinson’s claim that HIV tests are invalid because HIV has never been isolated. When scientists provided evidence that HIV has been isolated, the demand changed; Hodgkinson argued that the isolated virus was “impure”. Denialists now demand that the virus be isolated in “pure form”, that is uncontaminated by proteins. The demand for a pure virus devoid of cellular proteins is impossible to meet as it defies the biological nature of viruses. Such shifting of the grounds of debate allows denialists to claim that they are the ones following the evidence, and it is the AIDS establishment – an alliance of careerist researchers and greedy drugs companies – who are propagating pseudoscience.

All denialism is entrenched in conspiracy thinking. A spectrum of such thinking motivates AIDS denialism, covering everything from a government conspiracy to invent HIV for genocide against Africans and gays to a pharmaceutical industry conspiracy to sell toxic drugs. One of my favourites is the flamboyant conspiracy thinking of vitamin entrepreneur Matthias Rath, who said “The people and the governments of the world have to decide whether they are ready to stop being manipulated by the pharmaceutical industry and embrace instead the scientific knowledge that is now available to fight the global HIV/AIDS epidemic with effective, safe and affordable natural means.” The “natural means” Rath is referring to, of course, are the useless vitamins that he peddles to the poor. Though Rath has now been prevented from marketing his phony cure in Africa, and famously lost his libel suit against Ben Goldacre when he exposed his fraudulent practices, great damage was done and he continues to agitate for AIDS denialism through his spurious Health Foundation.

But while some denialists are clearly charlatans out to make a quick buck out of other people’s misery, many are perfectly genuine, which is what makes them especially dangerous. They can be persuasive because they actually believe what they say. Evidence means nothing to them. Their thought process resembles what psychiatrists call an “encapsulated delusion”, where despite what appears to be otherwise rational thinking there is an intractable maladaptive belief system that is impermeable to contrary evidence. Many of these people have themselves been diagnosed with HIV, and cling to the hope that this is not a death sentence. This adds a particular poignancy to their claims. A potent irony also hangs over denialism; year on year AIDS deniers who have tested positive for HIV succumb to AIDS-related illnesses. The most visible of such cases was Christine Maggiore, the founder of the Alive and Well movement that claims there is no causal link between HIV and AIDS. Maggiore believed that HIV does not cause AIDS even after the AIDS-related death of her three-year-old daughter and right up until her own death of AIDS in 2008. AIDS denialists are therefore a mixed bag of rogue scientists, pseudoscientists, conspiracy theorists, and snake-oil salesmen. There are also vocal AIDS denialist activists, primarily HIV positive people who are in deep denial of their diagnosis and seek the insulating bubble offered by AIDS denialism.

So, what can we do about AIDS denialism? There will always be crazy people who say crazy things. AIDS denialists only do harm when people listen to them. The best defence against AIDS denialism is improved public understanding of science and medicine. We all need to know how to recognise cranks and crackpots and their sinister rhetorical devices. When searching for reliable information make sure it does not rely on old, most likely outdated, sources. Find credible sources of current information and trust them, but keep pressing them with questions. Familiarise yourself with the basic facts of HIV and AIDS and be sceptical of far-fetched conspiracies. Be informed and think critically, but don’t fall for global conspiracy hysteria or accept pseudoscience because that is what you want to hear. We know that drugs companies make huge profits, and that scientists rely on research grants and can be fallible. This does not mean there is a global conspiracy to misrepresent the science. AIDS researchers and the pharmaceutical industry, believe it or not, are in it to save lives.

And finally, hard as it might be for believers in free speech and open debate, if you encounter AIDS denialism, do not enter into a debate. AIDS denialists want to create the impression that there is a debate regarding HIV causing AIDS and debating feeds the illusion. This debate was exhausted years ago. Now it merely serves as a distraction from the ongoing struggle to explain how and why HIV causes AIDS and trying to prevent it. In the words of The Who, and the title of Richard Wilson’s excellent book on scepticism, “Don’t Get Fooled Again”.

To see the AIDS Denialist Hall of Fame, visit the article at New Humanist.

Seth Kalichman's book Denying AIDS: Conspiracy Theories, Pseudoscience, and Human Tragedy is published by Springer/Copernicus - all royalties from the book are donated to buy HIV treatments in Africa.

Warning about pseudo-scientific review of alternative AIDS medicines

Eduard Grebe — Thu, 12 Nov 2009 17:10:44 +0000

A website that is advertised via Google ads, is promoting alternative, unproven and untested medicines for the treatment of HIV. The website is http://www.hivsecrets.com. Upon registering with it, a report titled HIV Alternative Therapies Report is made freely available for download. This report is written by a Ms Shirley Wyand. Ms Wyand has no known expertise in the science of HIV/AIDS.

The report is replete with misconceptions. For example, it states, "Since Western medical science offers no cure and few treatments for AIDS, people living with HIV are open to other options, and a tradition of gathering and sharing treatment information already exists." On the contrary, antiretroviral treatment is a very effective chronic treatment for HIV. There are also many effective medicines that treat AIDS-related opportunistic infections. There are no alternative treatments for HIV that have been shown to be effective. Indeed, once a medicine is shown to be effective it is no longer an alternative one.

Another example of the report's misconceptions is that it promotes an untested product called Revivo tea. This products advertisements touting its efficacy for the treatment of HIV have recently been banned in South Africa by that country's Advertising Standards Authority.

We urge people with HIV to be extremely cautious about following any of Ms Wyand's advice.

Anthony Mbewu is made director of GFHR: Is this an appropriate appointment?

Eduard Grebe — Wed, 04 Nov 2009 12:55:35 +0000

Anthony Mbewu with Matthias RathAnthony Mbewu, the current President of the Medical Research Council of South Africa (MRC), has been appointed the Executive Director of the Swiss-based Global Forum for Health Research (GFHR).

The South African government under former President Mbeki and former Health Minister, Manto Tshabalala-Msimang, pursued an AIDS denialist ideology that was responsible for at least 300,000 premature deaths and tens of thousands of preventable HIV infections. [1-2] Mbeki and Tshabalala-Msimang were the main protagonists in this crime against humanity. But there were several politicians and civil servants whose actions and inactions helped extensively. Anthony Mbewu was one of them. An appointment to a top position in Geneva hardly seems appropriate for someone with his questionable track record. This included misrepresenting the relative importance of HIV as a cause of death, supporting the vitamin salesman Matthias Rath, playing down the known benefits of antiretroviral treatment, promoting absurd conspiratorialist thinking and over-promoting multi-vitamins and traditional medicine as potential responses to AIDS.

Matthias Rath, with the support of Tshabalala-Msimang, conducted unauthorised experiments on people with HIV, imported and distributed his products unlawfully and claimed multivitamins alone reversed the course of AIDS, in contrast to antiretrovirals which he claimed were toxic. Anthony Mbewu helped establish Rath's presence in South Africa.

Rath at the MRCIn 2004, Mbewu had a series of meetings with Rath that led to Rath giving a workshop and committing to pay R200,000 to the MRC, of which over R60,000 was eventually paid. The minutes of the meetings with Rath are illuminating. They include plans to run a clinical trial using multivitamins to treat cancer. At one point the minutes record Mbewu stating, “NAPWA (National Association of People with Aids) [is a] good group. TAC [Treatment Action Campaign] is paid by pharma cartel. NAPWA has an open mind and will be an great advocacy tool as a counter-balance to attack.” NAPWA was a corrupt organisation that served Manto Tshabalala-Msimang's interests by opposing antiretroviral treatment. TAC, the organisation that led the campaign for antiretrovirals, never received money from pharmaceutical companies and eventually won an interdict against Rath for propagating this claim.

The minutes are replete with pseudoscientific assertions and evince an AIDS denialist agenda. There is additional questionable behaviour: In one meeting Mbewu introduced Rath to Denova, a marketing company of which Mbewu's wife, Priscilla Reddy (also an MRC employee) was a director. [3] (This reference has links to meeting minutes, commitments to pay and photos of Rath and Mbewu.)

Mbewu presented on HIV to the Parliamentary Health Portfolio Committee on 16 March 2005 and stated:

The importance of nutrition in mitigating the impact of HIV and AIDS cannot be understated. The Tanzanian/Harvard University clinical trial by Fawzi et al published recently in the New England Journal of Medicine is a case in point. This blinded, randomised controlled clinical trial showed that amongst over 1000 HIV positive women; those assigned to receive daily multivitamin over the subsequent 5 years showed a 30% reduction in death and progression to AIDS compared to those who did not receive multivitamin. This implies that multivitamins can reduce the socioeconomic impact of HIV and AIDS by both reducing the annual death rate, as well as reducing the rate at which patients deteriorate to the point of needing active medical care. In addition, the widespread use of traditional medicines in AIDS could have direct benefit, if efficacious in reducing mortality; as well as indirect benefit in stimulating the industry of producing and distributing natural medicines.

He then stated:

Little is known about the length of survival of patients on antiretroviral therapy in resource poor settings. Data from ACTG studies in the USA, using regimens similar to those we use in South Africa suggest that median survival once started on ARVs is likely to be of the order of several years but this is very tentative.

As the TAC has explained, “these statements are misleading. He has contrasted multivitamins with antiretrovirals and in effect argued that there is more reliable evidence of the usefulness of multivitamins than antiretrovirals. This is false. The opposite is actually the case. Little is known of the effect of multivitamins on people with HIV. While Mbewu correctly identifies that a Tanzanian study found them to be beneficial, he fails to point out that these benefits were small relative to antiretrovirals. He claims little 'is known about the length of survival of patients on antiretroviral therapy in resource poor settings', while actually little is known about the survival benefits of multivitamins and a lot is known about the survival benefits of antiretrovirals in resource poor settings.” [4]

Mbewu and Rath enjoying dinnerMbewu also cast doubt on the size of the AIDS epidemic at a point when denialist scepticism was crucial to President Mbeki's resistance to introducing ARVs. He has been quoted stating, “The nation is in poor health, with just as many if not more deaths from heart disease and strokes than AIDS ... AIDS is a major problem, but heart disease and strokes are much bigger.” [5] Yet the claim that “heart disease and strokes are” a much bigger problem than AIDS had been shown to be false by a report published by the MRC. [6] (See also Professor Solly Benatar's criticisms of Mbewu's statements about AIDS mortality. [7])

The GFHR press release announcing Mbewu's appointment describes one of his achievements: “In 2003 he chaired the Task team that developed South Africa’s Comprehensive Care, Management and Treatment for HIV and AIDS programme that has enrolled 871 914 patients on antiretroviral therapy.” [8]

The statement is either cynical or callous. It shows a poor knowledge of the history of AIDS denialism in South Africa and appears designed to whitewash Mbewu's discreditable role in fostering it. This task team was appointed after a massive campaign by civil society led by the Treatment Action Campaign (TAC) to get the South African government to develop a treatment plan. It included several large marches as well as civil disobedience in which activists were beaten up, arrested and sprayed with water cannons. Finally the Cabinet relented and while Mbeki was out of the country, it ordered Tshabalala-Msimang to produce a treatment plan. Mbewu was appointed to head the task team by Tshabalala-Msimang because he was a politically reliable ally, the commissar whose job it was to ensure that the people doing the committee's real work were watched and controlled (thankfully not very successfully). To imply that Mbewu was responsible for South Africa's antiretroviral programme is a grave insult to the people who actually made the programme happen. The mealy-mouthed language and nutritional pseudoscience that made it into the report were Mbewu's doing.

GFHR describes itself as “an independent, international organization committed to demonstrating the essential role of research and innovation for health and health equity, benefiting poor and marginalized populations.” We question whether the appointment of Anthony Mbewu is consistent with that mission and call on GFHR to require Mbewu to account for his questionable and discreditable history.

References

1. Nattrass, N. 2008. AIDS and the Scientific Governance of Medicine in Post-Apartheid South Africa. African Affairs 2008 107(427):157-176. http://afraf.oxfordjournals.org/cgi/content/abstract/107/427/157 ^back^

2. Chigwedere, P. et al. 2008. Estimating the Lost Benefits of Antiretroviral Drug Use in South Africa. JAIDS Journal of Acquired Immune Deficiency Syndromes. 49(4):410-415, December 1, 2008. http://journals.lww.com/jaids/pages/articleviewer.aspx?year=2008&issue=1... ^back^

3. TAC. 2006. Release of Documents showing collusion between some government officials, including MRC Head Anthony Mbewu, and Matthias Rath. http://www.tac.org.za/community/node/2203 ^back^

4. TAC. 2006. Submission to African Peer Review Mechanism. http://www.tac.org.za/Documents/AfricanPeerReviewMechanismReportFinal-20... ^back^

5. Pretoria News, 17/2/2005. Quoted in TAC Submission to African Peer Review Mechanism. ^back^

6. Dorrington et al. 2001. The impact of HIV/AIDS on adult mortality in South Africa. http://www.hst.org.za/publications/452 ^back^

7. SAPA. 2005. MRC Man's statement supports AIDS denial. http://70.84.171.10/~etools/newsbrief/2005/news0211.txt ^back^

8. Global Forum for Health Research. 2009. Appointment of new Executive Director: Prominent South African researcher to head Global Forum for Health Research http://www.globalforumhealth.org/Media-Publications/Archive-news/Appoint... ^back^

"House of Numbers" Lies about Research Findings on T Cells Destruction and AIDS

Eduard Grebe — Mon, 02 Nov 2009 12:39:48 +0000

by Jeanne Bergman

The lynchpin of Brent Leung’s argument in “House of Numbers” that HIV does not cause AIDS is the headline of a 2007 article on ScienceDaily.com that read, “Sudden Loss Of T Cells Is Not Trigger For AIDS, New Study Suggests.” [1] The screen shows the article’s headline and first paragraphs for 12 seconds (a very long time in “House of Numbers”), while Leung, in a voice-over, intones, “In late 2007, ScienceDaily reported that three prominent research teams had published papers in the Journal of Immunology, challenging the theory that the sudden loss of T-cells triggers disease and AIDS.” Since T cell destruction is understood to be the primary mechanism by which HIV destroys the immune system, this seems to seriously challenge the HIV/AIDS paradigm.

The film then cuts to a clip of researcher John P. Moore saying, “The details of HIV pathogenesis, how HIV kills people, are still being worked out.” The placement of this interview fragment implies that Moore would agree that T cell destruction does not lead to AIDS and death (though, of course, he does not agree: JPM – personal communication). Next, Leung is shown in a lab, theorizing that, “If the sudden loss of T-cells in HIV positive individuals can’t explain why people get disease, then there must be co-factors that cause people to get sick and die. Or, factors that have absolutely nothing to do with HIV.” And the film goes on to propose other causes for AIDS—poverty, poppers, AZT.

But the research Leung cites to claim that T cell loss does not cause AIDS does not say what Leung says it did. On the contrary, it affirms that in humans T cell destruction leads to AIDS and death. The document on the screen was indeed from ScienceDaily, a popular science news website. However, the headline and first paragraph of that article, which was itself based on a press release from Tulane University, did not accurately represent the research: notably, it failed to mention that the research was done with non-human primates. Leung and his crew disregarded the rest of the ScienceDaily article, which clearly recorded that non-human primates were used and stated that the particular strain of SIV infecting these particular simian species behaves differently from HIV in humans. (Some other strains of SIV do cause AIDS in other simian species, notably in macaques) In the simian species used in this particular study, the animals rebound from the T cell destruction caused by the infecting virus, whereas humans generally don’t when they are infected with HIV. Leung also ignored the actual Journal of Immunology articles that ScienceDaily linked to—which is remarkable since his entire case against HIV’s causality rests on them. [2]

The articles misrepresented by Leung said that three teams of researchers studied SIV-infected sooty mangabeys, rhesus macaques, and African green monkeys, respectively, and found that soory mangabeys and African greens have non-pathogenic infections: they can recover from T cell depletion, which is why they do not get AIDS. (Rhesus do progress rapidly to AIDS.) The researchers explicitly contrasted non-human primate T cell recovery with the disease progress in HIV-infected human beings, who cannot recover from T cell depletion without treatment, and who therefore progress to AIDS and death. The three research teams suggest that while some non-human primates have evolved to adapt to the virus over many centuries, it is still new in humans: we have not yet evolved to recover from T cell destruction. The researchers see their findings as suggestive for therapies to control immune system activation and promote recovery from HIV-related T cell destruction.

We contacted ScienceDaily and they have corrected the misleading headline and paragraph. The headline now reads, “Progression Of SIV Infection In Monkeys Points To Differences Between Human And Simian Forms Of AIDS.” [3] The summary of the research clarifies the distinction between the virus in humans and simians:

Another major question raised by the study is why monkeys with SIV, unlike HIV-positive humans, are generally resistant to progression to AIDS after infection with the virus.

The answer, the authors propose, is that thousands of years of host/virus co- adaptation has enabled monkeys, the natural hosts of SIV, to effectively limit T cell immune activation and apoptosis, a mechanism that leads to progression of the disease. By contrast, humans, who were introduced to the virus fairly recently, have not had the opportunity to develop such protective adaptations.

ScienceDaily has also added an Editor's Note:

This story has been modified from its original version, which can be accessed here:http://web.archive.org/web/*/http://www.sciencedaily.com/releases/2007/09/070923193631.htm (via the Internet Archive's Wayback Machine). This version clarifies that the research described in the story examined the differences in how the simian and human forms of AIDS progress. The purpose of the story was NOT meant to suggest that the sudden loss of T cells is not the trigger of AIDS in humans, nor was there any intent to support the erroneous belief that HIV somehow does not cause AIDS. We regret any confusion that this may have caused. Links to the abstracts of the journal papers referred to above are provided below.

There is very little actual research cited in “House of Numbers.” It is shocking that Leung so radically misrepresented the only legitimate “evidence” for his HIV denialist theory, and that his source in fact affirms that HIV destroys T cells in humans, causing AIDS.

November 1, 2009

Notes

1. Tulane University (2007, September 26). Sudden Loss Of T Cells Is Not Trigger For AIDS, New Study Suggests. ScienceDaily. ^back^

2. Ivona V. Pandrea, Rajeev Gautam, Ruy M. Ribeiro, Jason M. Brenchley, Isolde F. Butler, Melissa Pattison, Terri Rasmussen, Preston A. Marx, Guido Silvestri, Andrew A. Lackner, Alan S. Perelson, Daniel C. Douek, Ronald S. Veazey, and Cristian Apetrei. Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence. Journal of Immunology, 2007; 179: 3035-3046.

Shari N. Gordon, Nichole R. Klatt, Steven E. Bosinger, Jason M. Brenchley, Jeffrey M. Milush, Jessica C. Engram, Richard M. Dunham, Mirko Paiardini, Sara Klucking, Ali Danesh, Elizabeth A. Strobert, Cristian Apetrei, Ivona V. Pandrea, David Kelvin, Daniel C. Douek, Silvija I. Staprans, Donald L. Sodora, and Guido Silvestri. Severe Depletion of Mucosal CD4+ T Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys. Journal of Immunology, 2007; 179: 3026-3034.

Jeffrey M. Milush, Jacqueline D. Reeves, Shari N. Gordon, Dejiang Zhou, Alagar Muthukumar, David A. Kosub, Elizabeth Chacko, Luis D. Giavedoni, Chris C. Ibegbu, Kelly S. Cole, John L. Miamidian, Mirko Paiardini, Ashley P. Barry, Silvija I. Staprans, Guido Silvestri, and Donald L. Sodora. Virally Induced CD4+ T Cell Depletion Is Not Sufficient to Induce AIDS in a Natural Host. Journal of Immunology, 2007; 179: 3047-3056. ^back^

3. Tulane University (2007, September 26). Progression Of SIV Infection In Monkeys Points To Differences Between Human And Simian Forms Of AIDS. ScienceDaily. ^back^

Maggiore's labs

Eduard Grebe — Sun, 01 Nov 2009 07:00:00 +0000

"House of Numbers" offers new information about the late Christine Maggiore's experience with HIV testing. In the movie, her oral narrative and the dated lab reports on screen simply don't line up. What the film clearly shows by including the lab work is that Maggiore was HIV infected, and the reports suggest that her immune system controlled the virus well for some time. Commentary are placed in the blocks.

Christine Maggiore: “In 1992, I was encouraged by a doctor to take what’s called an HIV test as a mater of social responsibility, and I was shocked and devastated and horrified when the results came back positive. It was one of those moments that everyone fears their whole life. A week later, I take the same test to an AIDS specialist. He looks and says, this isn’t a positive test. I don’t know what this test means.”

The screen shows a lab report from Patricia O’Connell, NP, for Christine Maggiore, dated 02/24/92. Resolution is not good, but it looks like two bands—P24 and P120/160—of a Western Blot were reactive, the rest non-reactive. This VERY clearly is a positive test. The test interpretation instructions are below and she has a positive WB according to this test’s criteria (p24 and gp120).

Maggiore: “So I take the test again, and this time my results come back from the lab marked “’indeterminate.”

The screen shows part of a lab report in, with “Western blot” and “indeterminate” highlighted in yellow—bands from only 2 (GAG, ENV) of 3 groups positive. But it appears to have been a pretty thorough set of tests, include T-4 count etc. Interesting how shot is edited: column headings missing, no date, etc. NB: The second WB has different criteria – the same two bands are present but without a POL band this test will not be listed as positive. CD4 count (1040) and CD4/CD8 ratio (1.28) are comparable to an uninfected person and typical of someone who is controlling the virus very well immunologically. No date though.

Some denialists claim Maggiore refused treatment at this time, but with this CD4 count it would never have been offered. Indeed, Maggiore herself characterized the advice of her doctor at the time as 'wait 'til you get sick, and then we'll give you AZT.' This quote also contradicts another denialist myth, that asymptomatic people with HIV were routinely offered antiretroviral treatment.

Maggiore: “I’m faced with a decision: do I want to wait six weeks to test again, or do it right away? I opted for right away. My results that time come back positive.”

The screen shows another lab report, dated 9/23/93—nineteen months later. This is hardly “right away.” It is REACTIVE on every line—8 of 8 bands positive.

Maggiore: “Took it again, came back negative.”

The screen shows a lab report dated 08/09/93-six weeks BEFORE the test shown above. So the sequence of events she is narrating is not supported by the paperwork shown. The name on this report is Christina Maggiore, not Christine. Only a fragment is visible. NB: can’t tell if this one is an ELISA screen or a WB. It looks like an ELISA.

Maggiore: “I took it again—positive”

On screen, another lab report dated Sept. 29, 1993. This seems to be the one she took “right away”—six days after the solidly positive test. Sept 29, 93: HIV-1 EcG Confirmation [can’t read] Positive HIV-1 Ab 3g (?0 EIA 9.9 ]

Maggiore: "I’m very much opposed to the concept of mandatory testing of any population, because the tests are scientifically shown to be unreliable and inaccurate."

South Africa needs an HIV/AIDS truth commission

Eduard Grebe — Tue, 27 Oct 2009 22:44:17 +0000

Salim Abdool Karim with his wife and collaborator Quarraisha Abdool Karim
Photo credit: CAPRISAIn this article prominent South African AIDS researcher, Prof Salim S. Abdool Karim, calls for a truth commission to account for South Africa's past HIV/AIDS denialist policies and rebuild trust:

The HIV/AIDS epidemic is one of the greatest challenges facing post-democracy South Africa. In 2007, the country, which is home to less than one per cent of the world's population, carried 17 per cent of the global burden of HIV infection — and the virus continues to spread relentlessly.

The government's response to the epidemic during the last decade has contributed to this disproportionate burden. It not only questioned the reliability of HIV testing, the safety and efficacy of antiretroviral drugs and the accuracy of statistics on AIDS-related morbidity and mortality, but also the very premise that HIV causes AIDS.

Deliberate attempts were made to undermine scientific evidence as the basis for action and to place politics at odds with science. President Thabo Mbeki's AIDS Advisory Panel, set up in 2000, marked a low point in the government's relationship with scientists when he asked AIDS scientists to engage AIDS 'denialists' in a debate for political adjudication.

Preventable deaths

The impact of these policies was very damaging. The government delayed the implementation of nevirapine — an antiretroviral drug proven to prevent mother-to-child transmission of HIV — which resulted in hundreds of thousands of newborns becoming infected unnecessarily. Researchers at Harvard University estimate that between 2000 and 2005, 330,000 lives were lost to HIV/AIDS and 35,000 babies were born with the virus because of government inaction and failure to provide lifesaving drugs.

AIDS activists have repeatedly had to challenge health service providers, government and pharmaceutical companies. Through petitions, marches, mobilising communities and legal action they have sought to bring more treatment to poor people.

But the change in government leadership last year has created new hope that the country will rise to the challenges posed by HIV/AIDS. President Jacob Zuma's 2009 State of the Nation Address boldly stated: "We must work together to improve the implementation of the Comprehensive Plan for the Treatment, Management and Care of HIV and AIDS so as to reduce the rate of new HIV infections by 50 per cent by the year 2011. We want to reach 80 per cent of those in need of ARV [antiretroviral] treatment also by 2011."

Yet, while these statements are welcome, should we simply forget the past and accept that it was unfortunate — but there is nothing we can do about it now? To simply ignore the actions that led to hundreds of thousands of avoidable deaths would be to condone them and lay South Africa open to history repeating itself.

Call for a commission

South Africa needs an HIV/AIDS truth commission as a vital step towards establishing what happened and why, including detailed estimates of how many people died.

It is particularly important to hear directly from the decision-makers and to gather personal testimonies from all parties involved on how the damaging policies took hold in a democracy, where government should be accountable to the public for its actions.

The commission would also help us understand how to prevent the situation from happening again and would give the many people who lost loved ones to AIDS an explanation for why they died unnecessarily.

It is also needed to rebuild trust among people working against HIV/AIDS in South Africa, including those in research, government, health and local communities.

Simply establishing the truth is an important step. But for real reconciliation, the truth must also be made public and open to scrutiny before we can move on.

As South Africa starts building a new era in its response to the HIV/AIDS epidemic, we must work together — government, scientists, civil society and community organisations. It will take all our efforts — unimpaired by any ill-feeling or hurt from the past — to build a constructive foundation for tackling this devastating enemy.

Salim S. Abdool Karim is director of the Centre for the AIDS Programme of Research in South Africa at the University of KwaZulu-Natal. He was a member of Thabo Mbeki's AIDS Advisory Panel.

This article originally appeared on SciDev.net. It is republished in accordance with the Creative Commons Attribution 2.0 licence.

Reviled, Yes. Genius? Not So Much.

Eduard Grebe — Mon, 19 Oct 2009 15:06:58 +0000

Newsweek Exposes Duesberg’s Psychopathology

by Jeanne Bergman for AIDStruth.org

Peter Duesberg:
Photo by Seth Kalichman

"The whole dissident idea attracts a lot of crazies. And then all of a sudden, without realizing it, you've become one of them."

—Peter Duesberg

Newsweek this week published a strange and very revealing profile of the HIV über-denialist Peter Duesberg by Jeneen Interlandi (“The World’s Most Reviled Genius: Can the Scientist Who Denies the Cause of AIDS Be Trusted to Cure Cancer?” Oct. 19, 2009, pp. 44-48). The article asks if Duesberg’s aneuploidy theory of cancer may have some real promise that is being ignored because he has completely destroyed any scientific credibility he ever had by refusing to acknowledge that he was wrong about HIV and AIDS. (The short answer to this question is simply: no. Aneuploidy isn’t being ignored, much better scientists than Duesberg are working on it, and it is unlikely to be the key to the cause or cure of cancers. [1]) More significantly, the piece reveals a lot about the character and pathology of the man behind the denialist movement.

Interlandi describes how Duesberg has “toiled in scientific purgatory” at Berkeley. An embarrassment to the University, he has been relegated to a crummy little lab in a shabby building, with no grant funding, no promising graduate students, and no respect from anyone—including other cancer researchers working on aneuploidy. He is no longer allowed to teach. Duesberg clearly understands that this follows from his failed theory that HIV is harmless. Interlandi identifies in him a core conflict between two equally disturbing character traits: “he craves a return to respectability, [and] he refuses to cede any ground to his adversaries.” (See AIDStruth’s article about his malignant narcissism.) But Duesberg seems unable to grasp that the contempt is the result of his refusal to accept the conclusive scientific evidence that HIV is the cause of AIDS, and of his persistent proselytizing of his disproven claims about HIV, AIDS and antiretrovirals, which has caused hundreds of thousands of unnecessary deaths, particularly in South Africa.

The Newsweek profile touches on the formative impact of Nazism on Duesberg, who grew up a privileged Catholic in fascist Germany, and the resulting attitudes he holds toward people who aren’t heterosexual white men. He degrades women and developmentally disabled people (both lack “all the IQ genes,” he told Interlandi, “half joking”). He calls black people Schwartzes (the German N-word) and gays “homos,” and describes both as evolutionary failures. [2] His assistant calls these “gaffes,” and says of Duesberg: “He’s just from a different era, when people actually talked like that.” Actually, only Nazis and other racists, homophobes and eugenicists talked like that. Decent people of any age didn’t, and don’t.

In an extraordinary instance of projective inversion, Duesberg likens himself to the victims of Nazism rather than to the perpetrators of the Holocaust. Paraphrasing his reflection on his professional marginalization, Interlandi writes that for Duesberg “Being cast out of the mainstream… is like being herded onto a train by the Gestapo, never to be seen again.” Duesberg said this while relaxing at Caffe Strada, across the street from the great university that has tolerated both his professional failures and his hate speech. It’s appalling that the University of California allows this bigot to occupy space and draw a salary at the taxpayers’ expense.

Duesberg illustrated both his delusional feeling of victimization and his lack of ethics and judgment with a story about conducting secret tumor experiments on mice that he and his assistant bought in local pet shops. The article notes that this violated University policy concerning the pre-approval, housing, and treatment of lab animals. It might have also mentioned how stupid it is: results from those experiments would never be meaningful or publishable since they came from a small number of out-bred mice. U.C. learned of the project and, Interlandi writes, “Despite Duesberg's pleas to let them finish up, the mice were confiscated and killed. The data were lost. ‘We are the pauper scientists,’ he says, recalling the incident. ‘Always begging on our knees. Ever since HIV.’" Again, Duesberg can only see his imagined persecution, and not his abject failure as a scientist.

Newsweek did its best to find legitimate defenders of Duesberg. Interlandi writes: “Even some scientists who don't agree with Duesberg say that he has been treated unfairly,” and she quotes Lancet editor Richard Horton: "The ideological assassinations that he has undergone will remain an embarrassing testament to the reactionary tendencies of modern science.” But Horton wrote this in 1996, thirteen years ago, when antiretroviral drugs were just coming on the market. With their success, and in light of the unnecessary infections and deaths for which Duesberg is responsible, any illusions that criticism of Duesberg is based on ideology rather that evidence can no longer be sustained.

Peter Duesberg is shunned by his fellow scientists not because he is stubborn or obnoxious. He is shunned because he has been the driving force behind the AIDS denialist movement. He influenced the South African government, under former President Thabo Mbeki, to adopt an AIDS denialist position and delay the implementation of antiretroviral treatment access. This resulted in over 350,000 avoidable deaths. There is no possibility of professional reprieve for a  scientist so consciously involved in such a grotesque outcome.

Endnotes

1. Is there any validity to the notion that Duesberg’s infamy has hindered exploration of a promising domain of cancer research? Not according to cancer research George Klein:

In some of the comments around the Newsweek article, and in similar Duesberg-contexts previously, I have noticed a slight hesitation by the virologists about the cancer-aneuploidy story, leaving open the possibility that this was a real contribution by Duesberg. It is not. Aneuploidy as an important factor in causing cancer was proposed 1910 by Boveri, as Duesberg correctly states. Later, it was not forgotten or ignored, as he claims, but was continuously on and off in the discourse. When he now proposes it as a major insight, reached by him, he is using exactly the same technique of distorting the facts and inflating himself, as he always does.

This is not a question of either oncogene mutations, or aneuploidy. Aneuploidy contributes to the malignization of the cells, by influencing the oncogenes and the suppressor genes. More variability is generated, and the cancer cell evolves more readily towards greater autonomy. But the rearrangement of the chromosomes does not alter the fact that it is the oncogenes and the suppressor genes that are the key players.

A correlation between the degree of aneuploidy and prognosis has been noticed by the German-Swedish pathologist Gert Auer and Duesberg may well have picked up the idea from him. Another German (German-American) cytogeneticist, Thomas Reed has similar ideas. In view of the fact that he invited Duesberg to speak at the NCI (according to him) he may be in support for Duesberg’s argument. But please notice that Duesberg’s input contributed is nothing but dialectics. I cannot see the slightest originality in his work or in his reasoning. The fact that he manages to make this appear as a new way of thinking that may advance the cancer problem, or, indeed, is more ingenious new thought contributed by a pariah (as Scientific American put it) or by a genius (Newsweek) is nothing but more Duesbergiana. It is amazing how well he plays this game and how he can find new consumers who have not yet realized that they are being misled.

George Klein MD, PhD, Professor Emeritus, Research Group Leader, Microbiology and Tumor Biology Center (MTC) Karolinska Institutet, Stockholm, Sweden. Personal communication, Oct. 12, 2009.

2. Duesberg frequently makes racist and sexism comments. In Nashville, TN, in April 2009, he referred to the impact of AIDS on “the populations of Africa, which”— snickering sarcastically—“we love so dearly,” It was clear that the prospect of millions of Africans dying didn’t bother him.

Real Answers to the Fake Questions in “House of Numbers”

Eduard Grebe — Fri, 11 Sep 2009 00:48:52 +0000

by Jeanne Bergman

“House of Numbers” is a film with a hidden agenda: it tries to make viewers doubt the reality that the virus called HIV exists and causes AIDS. It conceals this agenda behind a false veneer of honest inquiry. The filmmaker, Brent Leung, told a Huffington Post blogger: “I am not a denialist. Posing questions is very different than denying something. … I traveled the globe speaking with scientists, activists, clinicians, journalists and patients asking questions. My main goal? To educate myself and others, and to generate discussion on important questions that have not yet been answered.” But Leung is an HIV denialist—he has said he is “neutral” on the issue of HIV/AIDS, which means he rejects the evidence-based science that has conclusively proved the existence of HIV and its causative role in AIDS, a fatal disease syndrome. His film is supported and promoted only by denialists. And Leung in fact got the information he sought from the legitimate scientists, doctors, and advocates he interviewed, but he then edited it out of the film to deceive and confuse viewers. The audience is manipulated to reach the wrong answers to the questions he ask. Since Leung leaves his own positions unstated, he dodges accountability for the film’s potential impact—namely, that people might decide that they don’t need to protect themselves or others from being infected with HIV, or that people living with HIV might reject medical care and the medications that could keep them healthy.

Here we summarize the fake “questions” Leung raises in the film, and provide real, evidence-based answers.

“House of Numbers” asks if there is really a scientific consensus about HIV/AIDS.

The real answer is: YES. There is an overwhelming scientific consensus, based on incontrovertible evidence, that HIV exists and is the cause of AIDS. The scientific evidence has shown conclusively that HIV exists, is transmitted by the blood and sexual fluids of infected people, and gradually destroys the human immune system, resulting in AIDS, a syndrome manifesting in various diseases that healthy people fight off but that cause illness and ultimately death in people with advanced HIV disease. Before the advent of antiviral medications, people with advanced HIV disease had multiple, devastating infections and symptoms that would not seriously harm a person with a healthy immune system. Since 1981, over 25 million people worldwide have died from HIV/AIDS.

The makers of “House of Numbers” deceived legitimate HIV researchers, infectious disease doctors, and AIDS activists and philanthropists to get interviews with them, and they edited the footage to make it seem that there is disagreement that HIV exists and is the necessary cause of AIDS. These facts have been established in laboratories, clinically, and by epidemiology, and published in tens of thousands of peer-reviewed publications. We have much still to learn about HIV and AIDS, and some scientists don’t like each other, but no legitimate, qualified scientist or doctor questions the existence or consequences of the virus.

“House of Numbers” questions the reliability of the HIV test. Does the HIV antibody test actually tell us anything at all?

The real answer is: YES. HIV tests are extremely reliable, sensitive and specific. What is usually referred to as the “HIV test” is just one step in HIV screening and diagnosis. The ELISA or EIA test screens for the presence of HIV antibodies in blood or oral fluids. In any diagnostic tests, there is a balance between sensitivity (recognizing everyone who is a true positive, who has the virus or whatever is tested for) and specificity (recognizing everyone who is a true negative, who doesn’t have the virus or whatever is tested for). Greater sensitivity always means more false positives, because very sensitive test will react to some things that are not the virus as if it were. Although rare, HIV false positives can happen: they are caused by the ELISA test reacting to antibodies produced in pregnancy or from some autoimmune diseases. (It is not true, as denialists claim, that 70 different conditions can cause false positives. And false positives are a feature of all screening tests, not just those for HIV. For example, some men will test positive for pregnancy. It doesn’t mean they are pregnant, or that pregnancy tests are totally useless, or that pregnancy doesn’t exist: it only means that the test is calibrated to capture all pregnancies when used correctly because a false negative is a bigger problem than a false positive.)

The ELISA test for HIV is very sensitive, because it is used to screen the blood supply and any false negatives could result in the HIV infection of hundreds of people. A positive ELISA test is 99.5% sensitive after the “window period” following infection, before HIV antibodies have developed. Because there is a small risk of a false positive, every HIV test is then confirmed with a Western Blot test. The two-test protocol is over 99.9% accurate, and clinical monitoring of a patient’s viral load and immune system by a physician further confirms the diagnosis. Misdiagnoses of HIV infection resulting in inappropriate treatment with antiretroviral drugs are extremely rare and are considered malpractice. (In 2007, an HIV-negative Massachusetts woman, Audrey Serrano, sued and won $2.5 million in damages against the doctor who treated her for AIDS without confirming that she was HIV infected. The HIV testing technology is so good that there is simply no excuse for the mistake that her doctor made.)

“House of Numbers” questions the practice of asking about risk factors in testing and diagnosis. Don’t doctors just want to know if you are gay or a drug user, and isn’t the diagnosis really bogus?

The real answer is: NO. Questions about risk factors are part of good screening, diagnosis and care. One step in many HIV testing protocols is an interview to assess the individual’s risk of infection. This has value as for prevention education; in addition, knowledge about risk helps frame the accuracy of a screening test. For straightforward statistical reasons, the likelihood of a false positive is higher where there are no risk factors and low prevalence than where risk factors and prevalence are high. But every positive ELISA test is still confirmed by a Western Blot or other test. The HIV tester in the movie who says that an AIDS diagnosis would be dependent on risks being acknowledged in an interview was simply wrong. It seems likely that she was asked misleading questions by the interviewers.

“House of Numbers” questions why some people who are exposed to HIV are not infected. Maybe HIV isn’t communicable? Maybe it doesn’t exist?

The real answers are NO and NO. There is no virus for which exposure always leads to infection. It should be obvious that not everyone exposed to a pathogen gets sick. Everyone knows that when someone in an office has a cold, some co-workers will catch it, and others won’t: how many do get sick depends in part on what steps people take to reduce the possibility of transmission. In the film, denialist Liam Scheff says that scientists say that HIV is so infectious it “leaps off penises into vaginas.” That’s a lie—people knowledgeable about HIV are clear that HIV is a hard virus to get—but the consequences of infection are serious, so prevention is crucial. The likelihood that a virus, including HIV, will be transmitted depends on many factors, including the nature of the contact, the innate transmissibility of the particular virus, the nature of the exposure or contact, how long the virus survives outside the body, and the viral load of the person who has it (people recently infected have very high levels of virus, while people on antiretroviral HIV medications have low, sometimes undetectable levels). This may be complicated, but it isn’t unusual at all. (And be aware that many HIV denialists reject the existence not only of HIV but of ALL viruses, and even of the role of germs in disease!)

“House of Numbers” questions how one disease varies so much in different people. Could it be that there’s no such disease as AIDS?

The real answer is: No. HIV infection will, over time, destroy the immune system in almost all infected people. The immune system is then unable to fight off opportunistic infections that are present in the environment, and they will get sick and die. Different strains of the virus and different regionally endemic diseases that affect immune-compromised people account for geographic variation in HIV disease patterns. Once a person is infected, the rate of disease progression is affected by many factors—the strain of the virus and the person’s age, overall health, environment, nutrition.

Causality does not require uniformity to be demonstrated. While there is a period averaging ten years when an HIV-positive person is clinically asymptomatic (that is, has no major symptoms), there is great variation between people’s HIV disease progression, even within the same region or even household. For example, Christine Maggiore, an HIV-infected denialist, said she first tested positive in 1992: she survived without HIV treatment for fifteen years until her death from AIDS last December. Her daughter, to whom she transmitted the virus perinatally, survived only 3 ½ years without treatment: she died, tragically and unnecessarily, of AIDS in 2005.

“House of Numbers” asks if a disease that is diagnosed differently on different continents is really only one disease.

The real answer is: YES. It is all HIV disease, and how the doctors and public health officials in different countries decide to mark the point at which it becomes full-blown “AIDS” doesn’t alter the reality of the virus and its effects. The virus doesn’t care what you call it, and the progression of the untreated disease is not driven by, but only expressed in, diagnostic language. Differences in diagnostic criteria by region reflect lack of access to HIV testing technologies and different clinical approaches: specifically, most African countries’ health systems cannot afford HIV testing. That doesn’t mean that HIV doesn’t exist or that poverty causes AIDS. Where HIV tests are not available, an AIDS diagnosis obviously cannot include HIV status as an element of an AIDS diagnosis, so the diagnosis is based on the presence of opportunistic infections that would only afflict a person with a compromised immune system.

“House of Numbers” asks if the profits that pharmaceutical companies make from HIV drugs might in fact be the reason for the invention of HIV/AIDS.

The real answer is: NO. The fact that the pharmaceutical industry does make money from HIV drugs does not mean that there is no such thing as HIV or AIDS. From the earliest days of the epidemic, AIDS activists have demanded the pharmaceutical industry and the government do smarter, more ethical, and expanded research. Activists have fought for the rapid development of better, more effective, more tolerable, and more affordable treatments for HIV, and the current generation of antiretroviral drugs for HIV are effective and easily tolerated by most people living with the virus. But that can lead to complacency and even the HIV denialism showcased by “House of Numbers. ” We must continue to fight to make HIV treatment accessible and affordable to everyone who needs it, including through the production of generics and international trade strategies like compulsory licensing that cut into the drug companies’ profits. We need to fight for prevention strategies that are science-based and really work, like needle-exchange and condoms, and more fundamentally address the structural injustices that render some populations much more vulnerable to HIV, as well as to other diseases. And we must press for the development of vaccines, other prevention technologies like microbicides and post-exposure prophylaxis, and ultimately for a cure.

David Rasnick fails to declare conflict of interests

Eduard Grebe — Fri, 31 Jul 2009 18:47:51 +0000

David Rasnick is a co-author with Peter Duesberg and others of an article in Medical Hypothesis which claims that HIV is not the cause of AIDS. The abstract of the article states, "we call into question the claim that HIV antibody-positives would benefit from anti-HIV drugs, because these drugs are inevitably toxic and because there is as yet no proof that HIV causes AIDS." [1]

We note an undeclared conflict of interests in this article by David Rasnick. Rasnick was a researcher for a company called the Rath Health Health Foundation Africa. This organisation promoted and distributed (and in terms of South African law, sold) micronutrient products as alternatives to antiretroviral treatment in South Africa. It also conducted an unauthorised clinical trial using these products as alternatives to antiretrovirals on people with HIV. The company never published the results of this trial in a peer-reviewed medical journal, but instead published adverts purporting to report the trial's results, a practice that is considered unethical in medical research. Rasnick is described in these adverts as one of the researchers on the trial.

A case was brought by the Treatment Action Campaign and South African Medical Association against the company's owner, Matthias Rath, the Rath Health Foundation Africa, Rasnick and others in the Cape High Court in which the court was requested to interdict the unauthorised trial from continuing. The court found in favour of the plaintiffs and ruled that the defendants, including Rasnick, had indeed conducted an unauthorised clinical trial. [2] Several deaths occurred on the trial which have been documented by the TAC and others. [3] This is not the first time Rasnick has been involved in academic misconduct. He has previously misrepresented his affiliation with the University of California Berkley. [4]

The Nuremberg code was established partly in response to Nazi experimentation on human subjects during World War II. It establishes the minimum standards experiments involving humans should adhere to. It states:

...

2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur ... [5]

The unauthorised trial in which Rasnick was involved breaches nearly every clause of the Nurember code, particularly those above. Proper informed consent from the trial participants was also not obtained. There can be few crimes by a medical researchers as heinous as running an unauthorised experiment on human beings. While the court ruling in South Africa was a civil one, there can be little doubt that Rasnick is guilty of a grievous crime for which he should be prosecuted.

References:

1. Duesberg, P.H., Nicholson, J.M., Rasnick, D., Fiala, C. & Bauer, H.H. HIV-AIDS hypothesis out of touch with South African AIDS - A new perspective. Med. Hypotheses (2009). doi:10.1016/j.mehy.2009.06.024 http://www.ncbi.nlm.nih.gov/pubmed/19619953

2. Zondi J. Judgment in TAC and Others v. Matthias Rath and Others. 2008. http://www.tac.org.za/community/files/file/TACAndSAMAVersusRathAndGovernmentJudgment.pdf
3. TAC. Analysis of deaths on Matthias Rath illegal clinical trial. 2005. http://www.tac.org.za/Documents/ns02_11_2005.htm
4. TAC. The Citizen's publicity for AIDS denialists is irresponsible. 2006. http://www.tac.org.za/community/node/2214
5. Nuremberg Code. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2, pp. 181-182.. Washington, D.C.: U.S. Government Printing Office, 1949. http://ohsr.od.nih.gov/guidelines/nuremberg.html

New myth debunked: HIV is an endogenous retrovirus

Eduard Grebe — Wed, 08 Jul 2009 21:14:43 +0000

Fact: HIV has been shown to be exogenous throughout 20+ years of research.

An endogenous retrovirus is one whose genetic material has been incorporated into that of the host. This happens when the genome of the virus incorporates itself into the chromosome of the host's sex cell (sperm or egg) – or its progenitor – and thus, upon fertilization becomes part of the normal genome found in every cell in the body of the host. Over time, the endogenous retroviral genome usually accumulates deleterious mutations rendering it incapable of productive infection. One myth used by denialists is that HIV is one of these endogenous retroviruses. However, several lines of evidence from the published scientific literature refute this claim, and prove that it is an exogenous virus, found only in CD4+ T-cells and a few other CD4+ cell types (such as macrophages) and not found in most other host cells.

Early evidence:

In the very first publication regarding the identification of HIV, Dr. Luc Montagnier described several experiments showing that HIV was exogenous. The controls used in his co-culture experiments, for example, did not produce a reverse transcriptase signal, only those cells exposed to infected patient lymphocytes. This indicates that the signal did not originate from the genome of the uninfected donor cells. The RT signal (and thus the virus) was able to be passed on to other uninfected lymphocyte cultures and resulted in a similar RT signal pattern. This passing on of the virus is another line of evidence that HIV is unlikely to be endogenous [1].

Southern Blots:

The southern blot is a method for probing for the presence of a specific DNA sequence within a DNA sample. In southern blot hybridization, a small segment of single-stranded DNA is hybridized to genomic DNA. There is nothing in the human genome that hybridizes at reasonable stringency levels (i.e. the specificity of the test) to probes made from HIV-1 or HIV-2 proviral genomes[2]. One study did find two very short sequences (192bp and ~30bp) with some similarity (<60% and 95% respectively) to parts of the HIV genome. However, these two sequences were detected only under very low stringency (low specificity) and no other sequences with similarity to HIV were found [3].

PCR:

In experiments using PCR (another method for detecting specific genetic sequences) in infected patients’ lymphocytes, PCR detects HIV in only a fraction of the infected donor’s T-Cells [4]. This alone is enough to demonstrate that HIV cannot be endogenous. An endogenous virus, by virtue of its past integration in host germ cells, would be detectable in all nucleated cells of the host. In other experiments, HIV DNA was found in the lymphocytes of patients but only very rarely in sperm cells [5]. The absence of HIV DNA from certain cell types in patients again refutes the idea that HIV is endogenous.

The Genome Projects:

The genome projects have been a valuable tool in the field of genetics and also refute the idea that HIV is endogenous. At the time this article was being written, only two examples existed in the scientific literature of endogenous lentiviruses in mammals: one in rabbits and one in lemurs [6][7]. All sequenced primate genomes (including several human genomes) show no endogenous lentiviral genomes.

Common Sense:

Some common sense combined with a brief look at infections would likewise indicate that HIV is not endogenous. If it were endogenous, sequences would be most similar between family members and most different between distantly related individuals. However, this is not the case. Europeans of non-West African descent have been identified with HIV-2 infection, despite HIV-2 being predominantly found in West Africa [8]. Conversely, many Africans have been infected by HIV-1. If one claims that HIV is endogenous, one therefore also claims that West Africans with HIV-2 infections are more closely related to non-West African Europeans with HIV-2 infection than they are to their HIV-1 infected countrymen. This is simply absurd.

References

1. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. Science. 1983 May 20;220(4599):868-71. PMID: 6189183

2. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Folks T, Benn S, Rabson A, Theodore T, Hoggan MD, Martin M, Lightfoote M, Sell K. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43. PMID: 2989831

3. Novel human endogenous sequences related to human immunodeficiency virus type 1. Horwitz MS, Boyce-Jacino MT, Faras AJ. J Virol. 1992 Apr;66(4):2170-9. PMID: 1548756

4. Sensitive detection of HIV DNA in T4 lymphocytes of infected individuals by polymerase chain reaction.

Hsia K, Spector SA; International Conference on AIDS. Int Conf AIDS. 1990 Jun 20-23; 6: 160

5. HIV-particles in spermatozoa of patients with AIDS and their transfer into the oocyte. Baccetti B, Benedetto A, Burrini AG, Collodel G, Ceccarini EC, Crisà N, Di Caro A, Estenoz M, Garbuglia AR, Massacesi A, et al. J Cell Biol. 1994 Nov;127(4):903-14. PMID: 7962075

6. Discovery and analysis of the first endogenous lentivirus. Aris Katzourakis, Michael Tristem, Oliver G. Pybus, and Robert J. Gifford Proc Natl Acad Sci U S A. 2007 April 10; 104(15): 6261–6265. PMCID: PMC1851024

7. Parallel Germline Infiltration of a Lentivirus in Two Malagasy Lemurs. Gilbert C, Maxfield DG, Goodman SM, Feschotte C, 2009 PLoS Genet 5(3): e1000425. doi:10.1371/journal.pgen.1000425

8. HIV-2 infection in 12 European residents : virus characteristics and disease progression. Van Der Ende M. E.; Schutten M.; Thaoi Duong LY; Gruters R. A.; Osterhaus A. D. M. E. AIDS ISSN 0269-9370 1996, vol. 10, no14, pp. 1649-1655 (23 ref.)

Justice After AIDS Denialism: Should There Be Prosecutions and Compensation?

Eduard Grebe — Wed, 01 Jul 2009 22:28:55 +0000

AIDSTruth member and Treatment Action Campaign treasurer Nathan Geffen writes in the Journal of Acquired Immune Deficiency Syndromes:

Edward Mabunda

Edward Mabunda died on April 9, 2003. At least another 600 people died of AIDS in South Africa that day.(1) Edward was just 36 years old. He left behind a wife and 3 children. He was also a leader in the Treatment Action Campaign (TAC). He became an icon of the movement because of the fiery poetry that he recited to thousands of people. His poems urged former President Thabo Mbeki to make antiretrovirals (ARVs) available in South Africa’s public health system. He died because he could not obtain these life-saving medicines in time.(2)

From 1999 to 2007, Mbeki and his Minister of Health Manto Tshabalala-Msimang obstructed and then undermined the implementation of highly active ARV treatment (HAART) and prevention of mother-to-child transmission of HIV in the public health system. Two studies, conducted independently of each other, conservatively calculated that over 300,000 people died because of Mbeki’s AIDS denialist policies.(3–5) Edward Mabunda was one of them. These studies could not account for additional deaths due to the promotion of quackery, often with the health minister’s support. They also did not consider the number of infections that occurred because of the confusion generated by the insipid state-funded prevention campaign and the messages by some outspoken Mbeki supporters dismissing the link between sex and HIV infection.(6) The Mbeki era also fostered a profound mistrust of scientific medicine, the consequences of which also cannot be quantified.

Read the full article in JAIDS.

Or, if you don't have a subscription, read it at Denying AIDS and other odditites.

Reference: JAIDS Journal of Acquired Immune Deficiency Syndromes: June 30, 2009 - Volume Publish Ahead of Print. doi: 10.1097/QAI.0b013e3181ab6da2

Clarification on false claims made in emails circulating on the Internet

Eduard Grebe — Mon, 22 Jun 2009 13:32:54 +0000

We have learnt that Dr Jim Murtagh has made false claims about his relationship with some members of aidstruth.org in email correspondence with AIDS denialists. We do not wish to be drawn into the squabbles of people not associated with us. Nevertheless, we print the following clarification to rectify confusion generated by Dr Murtagh's emails:

Dr Murtagh is not a member of aidstruth.org. We are not affiliated with him. The members of aidstruth.org can be found on our About page.
This website receives no funding other than the personal contributions of some of its members to cover hosting costs.
Contrary to Dr Murtagh's claims, neither the Treatment Action Campaign (TAC) nor any other organisation in which members of aidstruth.org have a leadership role support Dr Murtagh financially or materially.
No members of aidstruth.org were aware that Dr Murtagh would make false claims in emails. We find such behaviour repugnant.
No leaders of the TAC are involved with Dr Murtagh or his dealings.
Contrary to suggestions in Dr Murtagh's emails, a judgment of the Cape High Court has found no evidence that the TAC has any financial relationship with the pharmaceutical industry. On the contrary, the court found it unlikely that the TAC would have such a relationship. The same court interdicted an individual and two organisations for falsely claiming the organisation was funded by the pharmaceutical industry.

Clark Baker - Ex-cop and homophobic right-wing blogger

Eduard Grebe — Thu, 11 Jun 2009 13:40:45 +0000

by Jeanne Bergman

Clark Baker is a former Los Angeles police officer who was fired in 1991 after being convicted of battering a jaywalking immigrant. The conviction was later overturned on appeal—not on the facts of the case but on grounds of prosecutorial misconduct.^¹ Baker has since worked as a licensed private investigator, often, he says, without pay. Baker has a few blogs and websites where he posts his own reactionary opinions^² as well as pieces by other conservative conspiracy theorists.

Baker says that he knew nothing about HIV/AIDS until 2008, when, through his relationship with an obstetrician named Gil Mileikowsky, he became involved with members of the Semmelweis Society International (SSI), a small group of physicians opposed to the abuse of professional peer review. SSI was embroiled in controversy: Miliekowsky had engineered the giving of its “Clean Hands” award to denialists Celia Farber and Peter Duesberg and many members, when they learned that these are HIV denialists, objected. Baker, who has no training or professional experience in science or medicine and apparently no college education at all, muscled his way into control of Semmelweis and rocketed to the forefront of the HIV dissident movement’s scientific and strategic leadership.

Baker has given varied accounts of how he became involved in HIV denialism. He writes that SSI then-president Roland Chalifoux, an osteopathic neurosurgeon, asked him “to conduct an independent investigation of Farber and Prof. Duesberg, citing [Baker’s] investigative experience, independence, and almost complete lack of knowledge about HIV and AIDS.”^³ But in a panel presentation in Nashville in April, 2009, he said that an AIDS physician asked him to investigate allegations that denialist Peter

Duesberg is guilty of genocide for the AIDS deaths of millions in South Africa. When his investigation progressed, he said, that same physician tried to get him to stop, presumably because Baker supported the denialists. Baker’s stories don’t match up, but in any case, his “investigation” resulted in an incoherent and error-riddled “report” that he called “HIV, AIDS, and Gallo’s Egg.” He has posted it widely on denialist websites and right-wing blogs.

In “Gallo’s Egg,” Baker lurches back and forth between copying internal Semmelweis emails about Farber and Duesberg and, in his “Investigator’s Response” to the issues raised, regurgitating well-worn denialist falsehoods and misinterpreted anecdotes. Throughout the document, Baker demonstrates his complete lack of basic knowledge about disease processes, viruses, the immune system, HIV screening and diagnosis, scientific research and publication protocols, and medicine. Here is a small sample of his compound errors of fact and analysis from a much longer list:

Baker claims that HIV doesn’t cause AIDS in chimps, and therefore it can’t cause AIDS in humans. This canard is wrong both factually and logically.^⁴
Baker challenges the proven fact that HIV is spread through sex by citing Nancy Padian’s study, reiterating other denialists’ misinterpretations of her evidence, which shows that safer sex prevented transmission of HIV in a sample of serodiscordant heterosexual couples.

In search of evidence of a pharma-funded conspiracy, Baker contrasts the FDA’s decision to give Crixivan approval six weeks after Merck applied for it to “110 clinical tests before approving Splenda.” In fact, the FDA gave accelerated approval of Crixivan in 1996 after 14 clinical trials (clinical trials must precede the request for approval) and traditional approval in 1998, after additional longer and larger studies. ^⁵
Baker confuses the immune system’s creation of antibodies to external pathogens with “the autoimmunity response.”

Reviewing an internal Semmelweis email from member Kevin Kuritzky that describes a lecture by Duesberg, Baker concludes the “anecdote is doubtful,” because Duesberg teaches at Berkeley and Kuritzky was at Emory, “three time zones east.” Unfamiliar with academic settings, Baker may not know that professors often give lectures on campuses other than their own.^⁶
Baker improperly and randomly references single studies to make false claims. He charges, for example, that perinatal ARV prophylaxis “is dangerous for both mother and child,”^⁷ and cites just one 15-year-old AZT study. In fact, the evidence is overwhelming that ARVs effectively prevent vertical HIV transmission and pose no significant risk of harm to mother or baby.

Baker thinks the standard term “antiretroviral medications” is “Orwellian,” and that the “primary ‘medicine’ is AZT.” The term is an accurate description of the drugs’ purpose and effect, and, while some combination therapies still include AZT, zidovidine is neither “the primary medicine” nor is it toxic at currently prescribed dosages.
In an effort to dispute the accuracy of HIV testing, Baker writes: “To prevent terrorists from boarding planes (or HIV in our blood supply), HIV test sensitivities are set so that Jimmy’s orthodontics and Grandma’s titanium hips activate the alarms. Once those alarms sound, the tests brand them as suspected terrorists.” Baker’s thinking here is chaotic and disorganized—HIV screening tests react to the presence of antibodies in the bloodstream, not to metal, and are not used to screen for terrorists—but he is partially right to analogize the ELISA tests to pre-flight screening. What he doesn’t understand is that his analogy illustrates the screening function of the antibody test: it is not designed to diagnose HIV without confirmation. Both pass-through metal detectors and ELISA tests are highly sensitive screening technologies that react to potential problems that must then confirmed (or cleared) by additional tests. For HIV antibodies, the confirming HIV is the Western Blot (the gold standard), and for airport screening, a wand or pat search. In both cases, further positive results generate additional investigation.

Baker’s core thesis, which emerges only gradually and partially in “Gallo’s Egg” but that he states more aggressively elsewhere,^⁸ is that Dr. Robert Gallo’s work on HIV was fraudulent, and that the discovery of HIV and the determination that it causes AIDS by destroying the immune system was unsupported by evidence then and has not been replicated since. Baker is wrong on every one of these points. He doesn’t understand the nature of the controversy over the co-discovery of HIV by Gallo’s lab at the National Cancer Institutes and the Pasteur Institute’s Luc Montaignier and Françoise Barré-Sinoussi.^⁹ Baker apparently believes that Gallo’s discoveries were merely theories floated without evidence, and that they were never replicated. He refers to Gallo’s “original opinion” (as opposed to evidence-based findings) and claims that it is “disingenuous for any scientist to argue any research that is based upon Dr. Gallo’s theory without proof that HIV a) actually exists, b) kills white blood cells, and c) causes AIDS. Consensus, based upon unproven hearsay, is not proof.” He seems not to know that all of these things have indeed been proven, beyond any doubt. HIV has been isolated thousands of times since 1984, and that there is abundant, indeed overwhelming, published evidence that the retrovirus HIV actually exists (even Duesberg has shown this), and that HIV infection results in destruction of CD4+ T-cells (what Baker calls “white blood cells”). The result is a marked defect in the T-Helper arm of the immune system, without which opportunistic infections can rage unchecked.^¹⁰ This state is advanced HIV disease—AIDS—which, without treatment, will in almost all cases lead to death.^¹¹

Emboldened by the denialists’ enthusiastic admiration of “Gallo’s Egg,” Baker broadened his scientific theorizing. In a post on another of his websites, www.cwbpi.com, he reviews the narrative of HIV+ denialist Karri Stokely and concludes

that the antiretrovirals Combivir and Sustiva are actually addictive antidepressants—he specifies that they are SSRIs and MAOIs—because Ms. Stokely says that she was unwell for months after quitting treatment. “Intentional or not, by marketing this class of drugs (MAOIs and SSRIs) as ‘AIDS medications,’ the pharmaceutical industry has built into its HIV cocktails a mechanism that punishes HIV patients when they interrupt their drug use.”^¹² Incredibly, Baker seems actually not to know that the chemical composition and biological action of a medication are relevant to the classification of the drug. He does not know what kind of drugs Crixivan and Sustiva are, or what they do, or even why patients are urged to taper off many medications, not just antidepressants.

So what does Baker say is the cause of AIDS, if not HIV? “It’s a lifestyle disease,” he asserted in Nashville in April. And in a spasm of vicious homophobia on the Semmelweis website, which he took over and now uses as another of his personal blogs, he wrote that AIDS began when “a small group of promiscuous, addicted, nitrite-huffing, gonorrheal and syphilitic bath house veterans began to get sick.” ^¹³ “Faced with the imminent loss of funding, Gallo and his goons needed a new virus that they could frighten Americans with. At the same time, gay activists wanted the world to believe that their lifestyle had nothing to do with their symptoms. If lifestyle was blamed, individuals would be responsible.” ^¹⁴ Baker has exhumed the oldest and most stigmatizing lie about HIV disease: that gay men and other people get it not from an infectious pathogen but because they lead immoral, irresponsible lives. This scientifically illiterate homophobe is the man whom Duesberg, Farber, and the rest of the HIV denialists have embraced as their researcher, colleague and spokesperson.

Jeanne Bergman

AIDStruth.org

June 9, 2009

1 According to the L.A. Times, Baker’s conviction was overturned on appeal in 1994 when the Superior Court found that “the prosecutor improperly invited jurors to reform the Police Department after other LAPD officers were acquitted of beating Rodney King” just 8 months before. “The judges ruled that prosecutor David Sotelo's repeated references to the King case during an emotionally charged period had denied Baker a fair trial, and in effect made Sotelo an unsworn witness at the trial. The judges also found misconduct by Judge McBeth, saying she failed to curb Sotelo's remarks, and ruled that defense attorney Bob Wilson, by not objecting to the remarks, failed to provide effective counsel.” Ann W. O’Neill, “Court Voids Policeman's Conviction - Jurisprudence: Appeals panel throws out the case against a Valley traffic officer accused of assaulting a jaywalker.” L.A. Times, April 29, 1994.

2 See, for example, “Obama sows the Seeds of Fascism,” posted on Baker’s blog exlibhollywood.blogspot.com on May 2, 2009, or his tirade against affirmative action, Judge Sonia Sotomayor, and Barack Obama in “The Problem with Race, Empathy, and Social Justice,” posted on May 26, 2009.

3 exlibhollywood.blogspot.com; posted July 20, 2008.

4 Novembre, F.J. et al. Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1. Journal of Virology 71(5): 4086-4102. May 1997.

5 Not surprisingly, drugs urgently needed for life-threatening illnesses are handled differently by the FDA than are artificial sweeteners like Splenda. AIDS activists have pressured Pharma for expedited, responsive drug development protocols and access to affordable treatment from the earliest days of the epidemic. Baker lacks the most basic knowledge of the drug development and approval process.

6 Celia Farber, who told the NY Post’s gossip columnist that she is suing Kuritzsky and two others for libel, references the same email in the lawsuit in an attempt to impeach Kuritzsky’s truthfulness. She says Kuritzsky “falsely represented himself as a student of Dr. Duesberg” (posted at http://www.scienceguardian.com/blog/celia-farber-fights-back.htm). Clark Baker is proud of his close association to Celia Farber and has said that “evidence” he collected is the basis for her lawsuit. Baker and Farber are wrong: Kuritzsky didn’t write that he was a student of Duesberg’s—he just wrote that Duesberg gave a lecture. A competent journalist or investigator would have fact-checked this.

7 Emphasis in the original.

8 In a May 5, 2009, blog posting, Baker wrote that Gallo’s “unproven opinions have since become the basis for all of AIDS policy in the US and around the world at a cost that approaches $1 trillion in US taxpayer dollars since 1981. The fact that Dr. Gallo’s Institute of Human Virology still receives millions of research dollars annually despite having been found guilty of scientific misconduct in 1992 is equally troubling. But like Bernie Madoff’s pyramid scheme, Gallo’s initial fraud gave birth to a trillion dollar fraud scheme that is now simply too big to fail.”

9 At issue was whether Gallo had himself had first isolated the retrovirus, or if the retrovirus he found was from a sample sent to him by Montagnier that had contaminated Gallo’s culture. It has since been proven that Montagnier’s lab in fact first isolated HIV, using techniques developed by Gallo, and that Gallo was the first to show that HIV causes AIDS. Years later, the Office of Scientific Integrity Review, part of the US Department of Health and Human Services, concluded that Gallo had committed scientific misconduct by making statements about the French virus that were untrue, thereby promoting his own laboratory’s ascendance in HIV research. (HHS withdrew that finding in 1993, around the time Baker was appealing his conviction for battering a civilian.) For a thorough, if awkwardly written, overview of the history of the messy discovery of HIV see Anders Vahine’s “A Historical Reflection on the Discovery of Human Retroviruses,” Retrovirology 2009, 6:40 (www.retrovirology.com/content/6/1/40, and posted on www.AIDStruth.org.

10 Defects in the B-cell antibody producing arm of the immune system do not appear to be as severe as in the T-helper arm. Fungi, cancers, and certain viruses like CMV are characteristic of AIDS. For more on exactly how HIV damages the immune system and accurate responses to other denialist lies, see Nick Bennett’s posts on his blog, especially “Latest BMJ Rebuttal” on October 1, 2004, at http://aidsmyth.blogspot.com/2004_10_01_archive.html, and his June 8, 2009 post, “HIV Kills T Cells...And Doesn't Need Help to Do It” at http://aidsmyth.blogspot.com/2009/06/hiv-kills-t-cellsand-doesnt-need-he....

11 See http://www.avert.org/evidence.htm for a brief, cogent review of the proof that HIV exists and destroys the immune system.

12 www.cwbpi.com, posted May 25, 2009.

13 http://www.semmelweis.org/2009/06/02/doctors-without-boundaries/. Emphasis mine.

14 ibid.

A historical reflection on the discovery of human retroviruses

Eduard Grebe — Thu, 04 Jun 2009 00:03:36 +0000

by Anders Vahlne (Clinical Virology and Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden)

Originally published in Retrovirology 2009 6:40; doi:10.1186/1742-4690-6-40.

Abstract

The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4^thissue of Science in 1984.

Background

Unfortunately the omission of the American scientist Robert C. Gallo from the 2008 Nobel Prize in Medicine or Physiology for the discovery of HIV by many has been viewed as a final scientific verdict handed down by the Nobel committee of the Karolinska Institutet on an old controversy between the Institute Pasteur and NIH and that previous settlements were for political reasons only. Also, the decision to omit Gallo has resulted in the resurrection of false allegations in the media that Gallo and coworkers at NIH had rediscovered or even stolen the French HIV isolate previously sent to them from the Pasteur Institute. Thus, it could be interpreted as if the Nobel committee finally had put right an unjust settlement previously obtained between the French and American scientific groups. There is no doubt or controversy about the fact that the French group was first to isolate this new virus. This is what the Nobel committee chose to award.

Two years ago I had the privilege to painstakingly and thoroughly go through all the literature related to the discovery of HIV. Since the motivation for the Prize by the Nobel Committee is very limited and the fact that the Committee members cannot comment on how they came to their decision, I think it is important that the medical community gets the correct historical facts about this important discovery. Therefore, I have written this article. I would say that what I present below is a fair and accurate account on the events and work that led to the discovery of a new virus as the cause of AIDS. Regarding whom should get the credit for the discovery of HIV, this review should enable the reader to come to his or her own conclusion. Mine, however, is different from that of those of my fellow faculty members that presently make up the Nobel Committee for the Nobel Prize in Physiology or Medicine. I will here show that by going through the literature it is evident that Gallo's group was not only first to show that HIV is the cause of AIDS but that the French group had not been able to discover this new virus without the active assistance of, as well as, previous work by Gallo. It will also be evident that Gallo and his associates had no reason to "steal" any French isolate. Last year this journal published another account of the 2008 Nobel Prize [1].

Paving the way for the discovery of HIV

Isolation of a virus means infection, propagation and (usually cell free) transmission of an infectious agent in cultured cells. New viruses, for which there are no susceptible cells in culture, have lately also been detected solely by molecular techniques, e.g. hepatitis C virus by using a random-primed complementary DNA library from an infected patient (Michael Houghton) and subtypes of human papilloma viruses by using hybridization under low stringency and subsequent DNA cloning (Harald zur Hausen).

The difficulty in isolating a new virus is choosing the right cell culture and detection systems and to obtain specimens containing the virus. With a susceptible cell culture system and a detection system available, isolation of a new virus is not only possible but also rather straightforward. In the case of HIV, before the successful isolation of the first human retrovirus (human T-cell leukemia virus, now human T-cell lymphotropic virus type I; HTLV-I) by Robert C. Gallo [2], neither was at hand.

After the discovery of reverse transcriptase from animal oncogenic RNA viruses (then called oncorna viruses and now called retroviruses) a large number of publications on putative discoveries of retrovirus detections in human malignancies appeared in the early 1970-ties. However, they were all either owing to contaminations in the laboratories with animal retroviruses or the mitochondrial DNA-polymerase γ, the latter when the reports were based on reverse transcriptase activity alone. DNA-polymerase γ is a normal cellular DNA polymerase which uses RNA as a primer but not as a template. Therefore, like reverse transcriptase, the activity of DNA-polymerase γ was sensitive to a ribonuclease treatment [3-5]. This cellular enzyme was not known at the time. In 1972 Gallo's group [3] reported that stimulated normal human lymphocytes contained a ribonuclease sensitive DNA polymerase distinct from viral RNA-directed DNA polymerase, an enzyme that Gallo's group characterized further in a number of publications. The enzyme prefers Mn²⁺. Unlike DNA polymerases α and β, the preferred primer-template for DNA-polymerase γ is (dT)≅15·(A)n over (dT)≅15·(dA)n! This third cellular DNA polymerase was independently from Gallo discovered by Art Weissbach and they later named it DNA-polymerase γ[6].

From the numerous and erroneous reports on retroviruses in various human cancers, the notion of human cancer viruses became in ill repute and rather than talking of "human tumor viruses" people in science talked of "human rumor viruses". In fact, as narrated by Gallo in one of his reviews[7], when Gallo first submitted their report on HTLV-I to Journal of Virology it was rejected right away by the editor Robert Wagner "insisting that they should cease, and not continue to perpetuate the controversy, strongly implying that we all know human retroviruses do not exist".

In his quest to find a human retrovirus in lymphoma/leukemia Gallo developed sensitive and generalized techniques for the detection of reverse transcriptase to discriminate it from cellular DNA polymerases [8,9].

To isolate T cell lymphotropic viruses one needs to be able to culture T lymphocytes. Working with conditioned medium to grow lymphocytes, Gallo together with two of his post doctorial fellows Doris Morgan, Frank Ruscetti discovered T cell growth factor (TCGF) later named interleukin 2 (IL-2). Hence, the first report of IL-2/TCGF was by Robert Gallo was published in 1976 [10]. The first paper by Kendal A. Smith on IL-2/TCGF did not appear before 1978[11].

I sincerely doubt that anyone would have been looking for a retrovirus as the etiological agent for AIDS had HTLV-I not previously been isolated. I will therefore shortly recapitulate the history of the discovery of this virus.

The discovery of the first human retrovirus

Reverse transcriptase activity was detected by Gallo's group in a T-cell line established (using IL-2) from a patients diagnosed originally with mycosis fungoides in1979. To show that this was indeed a new human retrovirus Gallo and coworkers set out to show that the same virus could be isolated from primary tissue samples of the same patient by culturing primary T-cells with IL-2; demonstrate that the virus was novel, i.e., not any of the known animal retroviruses; show it could infect human T cells in vitro; demonstrate specific antibodies to the virus in the serum of the patient; demonstrate that proviral DNA could be found integrated in the DNA of the cells from which the virus was isolated; and provide evidence that this was not a one-time affair by showing serological evidence of specific antibodies not only in the patient but in some others as well.

Most or all these results were obtained by the time Gallo submitted the first paper to PNAS allowing it to quickly be followed with several other reports[12]. The paper on the first isolation of HTLV-I [2] was submitted (communicated) for publication in PNAS on August 4^th1980 and appeared in the December issue of the same year. The second paper from Gallo and his group (especially Bernard J. Poiesz, another post doctorial fellow) on the isolation of HTLV-I now from fresh cultured cells from a patient with Sezary T-cell leukemia was submitted to Nature on May 1st 1981 and appeared in the November 19th issue of that journal[13]. In the February 19th 1982 issue of Science (submitted October 6th 1981) Gallo's group [14] reported that five of six tested ATL patients in Japan had antibodies to HTLV-I (only HTLV at the time).

On the 26th of June 1981 (six months after the Poiesz et al. paper from Gallo's group was published) Hinuma et al. submitted (communicated) a paper to PNAS showing antibodies against an antigen in a T-cell line, MT-1 from a patient with adult T-cell leukemia (ATL), in all 44 patients with ATL examined and in 32 of 40 patients with malignant T-cell lymphomas using indirect immunofluorescence[15]. The antibodies were also detected in 26% of the healthy adults examined from ATL-endemic areas but in only a few of those examined from ATL-non-endemic areas. Extra-cellular type C virus particles were detected in pelleted cells of the MT-1 T-cell line. Hinuma called this virus adult T-cell leukemia virus (ATLV). Characterization of the virus as a retrovirus was published in the March issue of PNAS, submitted (communicated) November 23rd 1981. In this paper[16] also proviral DNA was detected in fresh peripheral lymphocytes from all of five patients with ATL but not in those from healthy adults. This paper was submitted more than a month later than the Gallo paper showing antibodies to HTLV-I in Japanese ATL patients.

On July 13th of 1981 Miyoshi et al. (Hinuma last author) submitted a paper to Nature (published December 24th 1981) on the transmission of virus from MT-1 cells (female) to cord blood cells of a male infant transforming (immortalizing) the latter cells[17].

In the November 4^th1982 issue of Nature Gallo's group together with the Japanese colleagues Nakao, Miyoshi, Minowada, Yoshida and Ito reported that HTLV-I and ATLV was one and the same virus[18] and decided to call both viruses HTLV-I.

As is evident from the above Gallo was truly the first to isolate the first known human retrovirus and to report it. In 1982, Gallo and co-workers reported the discovery of the second human retrovirus, HTLV-II, in a patient with hairy cell leukemia. However, no malignancy or other disease has yet been clearly linked to the infection of this virus.

The isolation of what is now called HIV-1 (will also be referred to as HIV, LAV, IDAV-1, IDAV-2, LAV-1, HTLV-III and ARV) and the demonstration of this virus as the cause of AIDS

In May of 1983 Françoise Barré-Sinoussi et al. published a paper in Science [19] describing the isolation of a putative new human retrovirus from the lymph gland of a patient suffering from persistent generalized lymphadenopathy, which is regarded as a precursor condition of AIDS. They called this new virus LAV (later LAV_BRU) for lymphadenopathy virus and BRU from the first three letters of the patient's last name. Since this has been viewed as a seminal paper for the discovery and characterization of HIV, I will here describe this paper in detail.

Cells from a lymph node of patient B.R.U. was cultured under the conditions described by Gallo [2,13], i.e. culture medium with T-cell growth factor (TCGF or IL-2), and were stimulated with phytohemaglutinin (PHA). They also added antiserum to human α-interferon to neutralize possible endogenous interferon. (The latter is not necessary, and is not used by others.) After three days, the culture was continued in the same medium without PHA. After 15 days in culture reverse transcriptase (RT) activity was detected in the culture supernatant, using the protocol by Gallo [2,13]. Importantly, the ionic conditions were the same as for isolating HTLV-I previously described by Gallo (1 and 2; in contrast to other animal retroviruses HTLV-I has a Mg²⁺-dependent and not Mn²⁺-dependent reverse transcriptase). Virus production continued for 15 days and decreased thereafter, in parallel with the decline of lymphocyte proliferation. A standard and routine procedure in clinical virology when trying to isolate a virus is to passage the cells to fresh ones, usually when the original cells start to die, and particularly if they do not yet show any signs of being infected. Hence, to show virus transmission, cells from patient B.R.U. after three days in culture were also co-cultured with lymphocytes from a healthy donor of the Blood Transfusion Center at the Pasteur Institute. Also with these co-cultures, RT could be detected after 15 days of culture (not before) and amounts of RT remained stable for 15 to 20 days. Transmission of cell-free supernatants from the original culture of B.R.U. cells was successfully obtained using 3-day-old cultures of T lymphocytes from two umbilical cords. There is no mentioning of cytopathic effects in any of the cultures or that fresh T lymphocytes from healthy donors were added to make the virus isolation possible or to save the virus isolate except for the virus transmission experiment described above.

The virus isolate had a density of 1.16 (same as HTLV-I) in a sucrose gradient. Electron micrographs of the virus from the umbilical cord lymphocytes were reported to be of typical C-type virus, i.e. with a spherical core (same as HTLV-I). Of note, HIV is a lenti retrovirus having a conical or cylindrical core structure and does not have type C virus morphology.

Two experiments were performed to distinguish the new isolate from HTLV-I. The first was by immunofluorescense using serum from the patient as well as a goat anti HTLV-I p24 (capsid protein) and mouse monoclonal anti HTLV-I p19 (matrix protein). The two latter anti-sera, as well as two HTLV-I producing cell lines were from Robert C. Gallo as acknowledged by the French group in the paper. The sera were tested against two different cultures of normal blood lymphocytes, against the two lines of HTLV-I producing cells, and against virus producing cells from the co-culture of T lymphocytes of patient B.R.U. and the healthy donor and against infected cord blood lymphocytes. In addition cells from a lymph node from a person (patient 2) who presented with multiple adenopathies and who had been in close contact with an AIDS case was also tested. No RT activity was detected in the latter patient's cultured lymphocytes. The anti-HTLV-I sera from Gallo (anti p19 and p24) reacted with the HTLV-I producing cell lines only. Serum from patient B.R.U. reacted with 90–100% of the HTLV-I producing cell lines and with 90–100% of the co-cultured cells from B.R.U and the healthy donor, as well as, the cells from patient 2. The B.R.U. serum reacted with only 0.5 to 2% of the infected umbilical cord lymphocytes. It is noteworthy that B.R.U.'s serum reacted with 90–100% of the co-cultured cells from B.R.U and the healthy donor since we know that only the CD4 positive cells should be infected. The B.R.U.'s serum also reacted with 90–100% of the HTLV-I producing cells! If this were to be due to a possible double infection with HIV and HTLV-I again only CD4 positive cells should be positive. More likely something unrelated to either HIV or HTLV-I was detected by the B.R.U. serum, in my opinion most probably mycoplasma, a common contaminant in cell culture. The 0.5 to 2% positive infected umbilical cord lymphocytes may indicate retrovirus-infected cells. However, the lack of reactivity with the p19 and p24 sera with these cells is not a proof that the B.R.U. virus was not HTLV-I. The few percentages of possibly positive cells could simply have been missed with the specific antibodies but detected with the patient's sera containing antibodies to all viral proteins. The paper does not present any photos of the fluorescent cells.

The other experiment performed to distinguish the new virus from HTLV-I was immunoprecipitation of lysates of infected cord lymphocytes, as well as, virus released from the infected cells with the same sera used for immunofluorescense and in addition serum from patient 2. Serum from B.R.U. and patient 2 (whose lymphocytes were RT negative) precipitated a protein of the apparent size of 25,000 from extracts of the infected cord lymphocytes and from the supernatants of these cells. Serum from a healthy donor did not precipitate this protein, nor did the anti HTLV-I p19 or p24 sera. The sera from B.R.U. and patient 2 did not precipitate the p25 protein from an extract of one of the HTLV-I producing cell lines. However, neither did the goat anti HTLV-I serum from what I can determine from the figure presented! Thus, there is no positive control indicating that they indeed had an HTLV antigen to precipitate. If the goat antiserum indeed precipitated a p24 protein from the HTLV-I producing cell extract, the band of p24 precipitated was extremely week, indicating that the serum was not very good at precipitating HTLV-I p24, at least not in the hands of Barré-Sinoussi and coworkers. The HTLV-I producing cells were all infected as opposed to only 0.5 to 2% of the cord blood cells. So, if the cord blood cells were infected with HTLV-I and not a new virus, the goat antiserum would still have had a hard time precipitating any protein! An appropriate control would have been a serum from a HTLV-I infected individual. The size of the protein they precipitated is in fact 24,000, the same as that of HTLV-I. The core protein of both HIV and HTLV-I is 24,000.

In reality, in my view there is no evidence whatsoever in this paper that a new human retrovirus has been isolated! With the data presented, the virus they isolated could well have been HTLV-I or in particular HTLV-II. The paper was obviously written in haste, as acknowledged by Montagnier[20], and contains numerous errors and omissions in the figures legends.

After having a first manuscript being rejected by Nature, Gallo suggested to Montagnier to send it to Science and even strongly endorsed the paper to the journal (the book of Nikolas Kontaratos shows a facsimile of Gallo's letter to the editor of Science[21]).

A more thorough description of the French isolate LAV from patient BRU and two new retrovirus isolates from two patients with AIDS was given at a Cold Spring Harbor meeting held in September of 1983. A proceedings, however not peer reviewed, from the meeting was published not until September of 1984[22]. The oral presentation by Luc Montagnier at this meeting is to my mind the first report on a new third human retrovirus, in that electron micrographs on the isolate LAV from patient BRU clearly showed virus with conical cores. A selective tropism of LAV to CD4 positive T-cells (as is the case for HTLV-I) was also demonstrated.

The first publication in a peer reviewed journal indicating the isolation of a new retrovirus, distinct from HTLV-I and HTLV-II, isolated from two siblings with hemophilia B of whom one with AIDS, appeared in Lancet in April of 1984 and was written by the French group[23]. Again the immunological and molecular characterization of the isolated virus does not convincingly separate the isolated virus from HTLV-I. However, an electron micrograph clearly depicts a virus with a lenti retrovirus type morphology having a cylindrical or conical core, distinctly different from the larger spherical core of HTLV-I, and HTLV-II. The paper, however, fails to conclusively link the new virus as the causative agent of AIDS.

In conclusion, by April of 1984 the Pasteur group headed by Luc Montagnier had reported on a new human T-lymphotropic retrovirus distinct from HTLV-I and HTLV-II as judged by morphology and which was present in a few patients with AIDS and lymphadenopathy, as well as, in people at risk of acquiring AIDS. The virus infected CD4-positive T-lymphocytes, the very cells affected in AIDS. Although clearly associated with AIDS, they had not yet shown that the new virus was an etiological agent, and the only one at that, of this new disease.

On May 4^thof 1984 four papers by Robert C. Gallo's group were published in Science describing a new human retrovirus virus as the probable cause of AIDS. All four papers were submitted the 30^thof March 1984. One paper[24] describes the isolation of the new virus from cultured lymphocytes obtained from 48 different individuals. The culturing technique was what had previously been described by Gallo and which Montagnier's group also used. The new cytopathic (large multinucleated cells) virus isolates were collectively designated HTLV-III and was characterized by having a Mg²⁺-dependent reverse transcriptase, being transmittable by co-cultivation of T cells with irradiated donor cells or with cell free fluids, having distinct morphology by electron microscopy, and by expressing specific viral antigens (indirect immune fluorescence) using a serum obtained from a patient with pre-AIDS (described in an adjoining papers 25 and 26; this serum did not react with cells infected with HTLV-I or HTLV-II), as well as, antisera prepared against purified, whole disrupted HTLV-III. The 48 HTLV-III isolates were obtained from 18 of 21 tested patients with unexplained lymphadenopathy and leukopenia, with an inverted T4/T8 lymphocyte ratio (designated pre-AIDS), 3 of 4 clinically normal mothers of juvenile AIDS patients, 3 of 8 juvenile AIDS patients, 13 of 43 adult AIDS patients with Kaposis sarcoma, 10 of 21 adults AIDS patients with opportunistic infections, and 1 of 22 clinically normal homosexual donors. Importantly, this homosexual donor, from whom HTLV-III was isolated, developed AIDS six month after the virus isolations were performed. This means that these isolations were performed not later than September of 1983. HTLV-III could not be isolated from any of 115 clinically normal heterosexual donors.

In a second accompanying paper [25] antibody reactivity to HTLV-III antigens in patients with pre-AIDS and AIDS was determined by an enzyme-linked immunosorbent assay (ELISA) as well as a Western electrophoretic blotting technique using a lysate of sucrose gradient purified HTLV-III from a cell line continuously producing HTLV-III. [26] as antigen. The number of sera that gave positive scores in the ELISA were: 43 of 49 (88%) of patients with AIDS (two of whom had developed AIDS after blood transfusion), 11 of 14 patients with pre-AIDS, 3 of 5 intravenous drug users (of which one positive was also homosexual), 6 of 17 homosexual men. It is noted in the paper that these homosexual men had been seeking medical assistance; they probably were not representative of the homosexual population. Out of 186 controls only one scored positive in the ELISA (1 of the 164 normal subjects). The controls also included 3 patients with hepatitis B virus infection, 1 with rheumatoid arthritis, 6 with systemic lupus erythematosus, 4 with acute mononucleosis, and 8 patients with lymphatic leukemias. Of the latter some were positive for HTLV-I. None of these 22 control patients scored positive in the ELISA or Western blot. Of note, in Western blot the antigen most prominently and commonly detected among all of the sera from AIDS patients had a molecular weight of 41,000 (now designated gp41). It was presumed that this is a virus envelope protein (which later turned out to be correct). Others, including myself, have later confirmed that gp41 is extremely reactive in ELISA of sera from HIV infected individuals. In fact we have found that an ELISA having as only antigen a peptide with the amino acids GKLICT, representing an epitope of gp41, reacts positively with the majority of sera from HIV infected individuals.

The French group did not detect gp41 in their immune precipitation studies using purified LAV. Their inability to detect this protein in their ELISA or immune precipitation experiments is probably the main reason that their positive scores with AIDS and pre-AIDS sera were so low. HIV is an enveloped virus and hence fragile. Most certainly they had lost the virus envelope in their purification of the virus.

Taken together, these two papers from Gallo's group for the first time convincingly demonstrated that AIDS was caused by a new human retrovirus distinct from HTLV-I and HTLV-II. It also provided with a blood test (ELISA) by which blood donors could be screened and a confirmation assay (Western blot) for those who tested positive in the ELISA. The authors speculate that the virus they found could well be the same virus that was previously detected by the French group, but direct comparisons had not yet been performed.

A third paper. [26] describes the establishment of cell lines continuously producing HTLV-III. A total of 51 single cell clones (designated H1 to H51) were obtained from a neoplastic aneuploid T-cell line (HUT-78). The clones were tested for susceptibility to concentrates of HTLV-III. All clones were susceptible and permissive for the virus, but virus yields and cell proliferation varied considerably. The best clones (H4 and H9) were used for the long-term propagation of HTLV-III from patients with AIDS and pre-AIDS. Five different isolates using the H4 or H9 clones are presented. Four were obtained by co-cultivating the patients T-cells with the H4 cells and one by infecting H9 cells with a cell free concentrated culture fluid harvested from T-cell cultures from a patient (W.T.) who had lymphadenopathy. One was from an AIDS patient from Haiti (R.F.) and four were from the US. In the paper they also report that some of the 48 isolates described in the accompanying paper[24] also could be propagated in the H4 and H9 clones. The importance of this paper is that for the first time it was shown that one could propagate HIV in large quantities as a source for antigen in a blood test, as well as, for in depth characterization of the virus. It was this paper, and the patent which was based upon it, that later caused the controversy between the NIH and the Pasteur Institute. It turned out that the HTLV-III producing H9 clone selected for the blood test was in fact a pick-up of a French HIV isolate sent to Gallo in September of 1983. This will be discussed later.

The fourth of the Gallo Science papers [27] describes a first attempt to serologically characterize HTLV-III using Western blot and sera from AIDS and pre-AIDS patients. The paper describes for the first time a virus protein of approximately 130,000 (in fact it is 120,000 and now designated gp120). Also a protein of 55,000 (p55) is described and correctly concluded to be a precursor protein for the capsid protein p24.

Lastly, a photomontage of electron micrographs of HTLV-I, HTLV-II, and HTLV-III with budding virus particles, immature virus particles and mature virus particles is shown. Although the budding and immature virus particles are very similar for all three viruses, the mature HTLV-III viruses are distinctive from those of HTLV-I and HTLV-II.

Three more papers on antibody reactivity to LAV/HTLV-III in patients with AIDS or pre-AIDS were published in the summer of 1984. June 9^th, Montagnier's group[28] published an ELISA based on purified virus particles. The presented results were: 18/48 (37.5%) of AIDS patients, 38/51 (74.5%) of pre-AIDS patients and 8/44 (18%) of homosexual men without pre-AIDS, but only one of 100 unselected blood donors were positive. In a note added in proof they claim that by modifying their assay now 75% of AIDS patients and 90% of pre-AIDS patients scored positive. In the Lancet issue of June 30^thGallo's group[29] publish their second report (the first being the one in Science above) on ELISA and Western blot confirmatory assay in a double-blind seroepidemiological study. The composite result of the two assays gave: 34 of 34 AIDS patients were positive (100%), 16 of 19 (84%) of lymphadenopathy (pre-AIDS), 3 of 14 (21%) at risk for AIDS, and none of 14 controls were positive. Lastly, Kalyanaraman et al. [30] published a paper the 20^thof July in Science submitted May 4^th1984. This paper was from Donald Francis group at the Center for Disease Control, Atlanta, in collaboration with Montagnier's group at Pasteur. The assay they used was based on immuno-precipitation. The positive scores were: 51 of 125 (41%) of AIDS patients; 81 of 113 pre-AIDS patients, 0 of CDC workers, and 0 of 189 random blood donors. Of 100 blood samples collected in 1978 from homosexual men in San Francisco, only one was positive as opposed to 12 of 50 such sera collected in 1984.

In the July 6^thissue of Science (submitted April 6^th1984), Donald Francis' group in collaboration with Montagnier's group reported on the isolation of a retrovirus from a blood donor-recipient pair with AIDS [31]. In an elegant experiment, using a competition radioimmunoassay they clearly show that the viruses they isolated were closely related to LAV but not to HTLV-I or HTLV-II. This is the first paper to show transmission of HIV-1 from one patient to another. This is also the first time, beside the electron microscopic pictures of LAV, Montagnier convincingly shows that LAV is antigenic distinct from HTLV-I.

On August 24^th1984 Jay Levy in San Francisco[32] published a paper in Science (submitted May 31^st) reporting that using the Gallo protocol they had isolated a retrovirus with lenti retrovirus type morphology designated ARV for AIDS associated retrovirus in 22 of 45 patients with AIDS. Positive virus cultures were also received from 5 of 10 patients with lymphadenopathy (pre-AIDS), 3 of 14 male sex partners of AIDS patients, 2 of 9 clinical healthy homosexual men, and 1 of 23 clinically healthy heterosexual men. When tested in immune fluorescence with slides containing acetone fixed cells infected with ARV, HTLV-I or LAV, 78/86 (91%) of AIDS patient's sera were positive to ARV infected cells, 22 of 40 (55%) to LAV, and 8 of 60 (13%) to HTLV-I. None of 56 controls reacted to any of the virus-infected cells. The fixed ARV infected cells were from a cell line (HUT-78) successfully established to continuously produce ARV.

The LAV/HTLV-IIIB contamination story and the patent feud between the Pasteur Institute and NIH

Right before the first public announcement by Barré-Sinoussi at a conference at Cold Spring Harbour in May of 1983 of the Pasteur group's findings, the Pasteur Institute filed a patent for the virus they had isolated. Before going public with the four Science papers, the NIH filed for a patent for the blood test described in one of the papers to be published in May of 1984. The United States patent office quickly allowed the American patent, shortly to be followed by allowances from European patent offices, and a number of American companies started to produce and sell blood tests. The approval of the Pasteur patent was delayed, principally because the French had not reduced their patent to practice, i.e. showed that they had a working blood test in the patent application. This led to a patent feud between the NIH and the Pasteur Institute starting in August of 1985. To solve this feud, the governments of both countries had to become involved. The patent fight came to an end on March 31^st, 1987, when President Ronald Reagan and French Prime Minister Jacques Chirac signed an agreement to settle the arguments. The financial outcome of the agreement, however, did not turn out to the satisfaction of the French, and when it became clear that the US patented blood test was based on a laboratory contamination of a French virus the deal was re-negotiated in 1994. It should be stated right away that neither of the scientists at the time stood to gain from respective patent.

The ground for the feud was the following. Montagnier sent his first isolate LAV_BRUto Gallo in July of 1983. In May of 1984 Gallo's coworker Sarngadharan brings one of Gallo's five HIV strains (HTLV-III_B) that grew well in a continuous cell line to Montagniers laboratory in Paris. In July of 1984 Montagnier sends Gallo a second sample of LAV_BRUsince Gallo had complained that the first didn't grew well at NIH. Gallo then found and reported[33] that HIV was extremely variable; every isolated strain was different from the other also when obtained from the same individual but at different times. However, the two strains LAV_BRU(received in July of 1984) and HTLV-III_Bisolated on either side of the Atlantic Ocean where strikingly similar. Gallo's reaction to this was that Montagnier must have contaminated his cultures with the American isolate, i.e. that the Pasteur group had had a so-called "pick-up" of HTLV-III_Binto his poorly replicating LAV_BRU. Gallo gave Montagnier a call, but the latter denied that this could have happened in his laboratory. Since the LAV_BRUobtained by other laboratories, before HTLV-III_Bhad been introduced to the Pasteur laboratory, had a genome more or less identical to the French isolate, it was concluded that the contamination must have happened in Gallo's laboratory. Gallo found this very strange, since LAV_BRUreplicated very poorly and could not be transferred to a continuously producing cell line like they had achieved with HTLV-III_B. On Sunday, November 19^th, 1989, the Chicago Tribune published a 16 pages account by journalist John Crewdson of the discovery of HIV. The article concludes that HTLV-III_Bis LAV_BRU. Crewdson implied in not so subtle words that Gallo had stolen the virus from the French. This started three separate investigations for scientific misconduct by Popovic and Gallo that didn't end until November of 1993.

The explanation came in 1992. Sequencing the original isolate LAV_BRUreceived in NIH in 1983, Gallo found that it was different from the LAV_BRUreceived in July of 1984. The original LAV_BRUwas as expected of the slowly replicating CCR5 co-receptor using genotype whereas LAV_BRUfrom 1984 was of the rapidly replicating CXCR4 using genotype. In fact the 1984 LAV_BRUwas identical to LAV_LAI. Thus, the contamination had originally occurred in the Pasteur laboratory. According to Montagnier at least six other laboratories received the LAI sample (under the name BRU) from his group and experienced the same contamination. [34]. Montagnier speculates that this was due to Mycoplasma pirum contamination of the cultures infected with LAV_LAI. In his review "A history of HIV discovery" in Science. [34] Montagnier writes: "This physical association makes a fraction of the LAI virus highly infectious, and, in fact, this fraction can be neutralized with antibodies against M. pirum. As mycoplasmas are common contaminents of cultured cells, an infectious pseudotype virus (LAI associated with M. pirum) may have caused several contaminations between 1983 and 1984 in different laboratories".

In Gallo's laboratory LAV_BRUhad contaminated a pool of viruses from different AIDS patients. Pooling viruses was the idea of Mika Popovic in order to get the "survival of the fittest" to grow out in the continuous cell line H9, a subclone of the HUT-78 cell line. The virus that grew best was named III_Bbecause it was from the B-pool of two pools in culture.

Many probably thought that the finding that a contamination had taken place already in the Pasteur laboratory was "convenient" for Gallo. However, to "steal" the French virus Gallo must have had a motive. One would have been that they couldn't culture any virus from AIDS patients and were becoming desperate. However, Gallo had already recognized that the French group was first to isolate a new retrovirus from AIDS patients. More so he endorsed the publication of the first Pasteur paper, which (although in my opinion erroneously) claimed so. Secondly, Gallo's group already had 48 (sic!) isolates many growing short term in their laboratory of which five were growing in continuous cell lines [24,26]. Gallo's misfortune was that he decided to choose the III_Bfor the blood test and for further characterization of the virus. Had he chosen a Haitian strain, which he also had growing long term in the laboratory at the time, we now know that he would have chosen a virus, which was as much of a prototype strain for HIV-1.

It has been questioned whether Gallo indeed had all those isolates. Considering that Gallo published this and that he and his laboratory was scrutinized for almost five years by three different investigations, had Gallo not had those isolates he would for sure have been found guilty of scientific misconduct and expelled from the NIH. Going through 13 foot high pile of Gallo's lab records including laboratory note-books, some 10,000 man hours of interviews with laboratory personal and other witnesses, all the Office of Research Integrity (ORI; a non-scientist office of government consisting of lawyers and administrators) could come up with in criticism was for Mika Popovic that he wrote "ND" in two occasions in one published table (in paper 25), and found him therefore guilty of scientific misconduct. The table legend didn't define "ND" and it was the ORI's understanding that "ND" meant, "not done" and that Popovic indeed had performed the experiment. However, Popovic insisted that by "ND" in his notebook he meant, "not determinable". The paper was written while Popovic was on holiday back in Czechoslovakia. Following Popovic's appeal to the Research Integrity Adjudications Panel the decision of ORI's was reversed. Gallo was temporarily criticized by the ORI for having written a sentence in the discussion of the same paper that LAV_BRUhad not yet been growing well enough to make possible comparisons with III_Bwhen in fact a technician of Popovic's had done so. These charges were later dropped by the ORI. In its decision on the Popovic case the Departmental Appeals Board's Research Integrity Adjudications Panel writes: "One might anticipate that from all this evidence, after all the sound and fury, there would be at last a residue of palpable wrongdoing. This is not the case". It is safe to say that whatever Gallo claimed he had, he had.

Conclusion

There is no doubt that Luc Montagnier's group at the Pasteur Institute in Paris was the first to isolate the causative agent of AIDS. Montagnier, however, got the idea to try to isolate a retrovirus indirectly from Robert Gallo and Myron Essex. The protocols he used for virus isolation and RT detection were developed by Robert Gallo and the reagents he used to discriminate the new virus from HTLV-I and HTLV-II were obtained from Robert Gallo. Moreover, it is well known that Francoise Barré-Sinoussi had spent time in Robert Gallo's laboratory to learn to culture lymphocytes. Robert Gallo was the first to convincingly show that the new human retrovirus (HIV) was the causative agent of AIDS, and the only one at that. He also was also the first to provide a blood test to screen blood donors for HIV infection. The rapid implementation of the latter in the US and Europe probably saved hundreds of thousands of lives.

References

View references at Retrovirology.

© 2009 Vahlne; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/6/1/40

The dangers of denying HIV: John Moore reviews Seth Kalichman's Denying AIDS in Nature

Eduard Grebe — Mon, 25 May 2009 15:08:00 +0000

Nature 459, 168 (14 May 2009) | doi:10.1038/459168a; Published online 13 May 2009

John P. Moore

Denying AIDS: Conspiracy Theories, Pseudoscience, and Human Tragedy

by Seth Kalichman

Springer: 2009. 205 pp. $25

Inadequate health policies in South Africa have reportedly led to some 330,000 unnecessary AIDS deaths and a spike in infant mortality, according to estimates by South African and US researchers. This carnage exceeds the death toll in Darfur, yet it has received far less attention. Seth Kalichman, a US clinical psychologist, shows in Denying AIDS how words can kill. His marvellous book should be read alongside Nicoli Nattrass's Mortal Combat, covering similar ground but from the perspective of a South African.

The tragic events in South Africa have been exacerbated by AIDS 'denialists' who, Kalichman alleges, assert that HIV is harmless and that antiretroviral drugs are toxic. The author discusses the psychology of denialism, which he says is "the outright rejection of science and medicine". He recounts the history of an HIV-infected US woman whose daughter died from an AIDS-related disease, and who recently died herself, to demonstrate the downward path from "ordinary psychological denial to malignant denial to denialism". Kalichman dismisses denialists' attempts to portray themselves as intellectually honourable dissidents who question accepted wisdom. He draws clear distinctions between dissidence and denialism; the latter, he says, is merely a destructive attempt to undermine the science.

These attitudes are not unique to HIV. Denialism, notes Kalichman, is "partly an outgrowth of a more general anti-science and anti-medicine movement". Groups that support intelligent design, doubt global warming, claim that vaccines cause autism, argue that cigarettes are safe, believe that the terrorist attacks of 11 September 2001 were an intelligence-agency plot or deny the Holocaust all use similar tactics.

Kalichman asserts that influential groups within the AIDS denialist movement include academics, pushers of 'quack' cures and supportive journalists. He describes the academics involved as "deranged and disgruntled university professors who turn to pseudoscience as a platform to gain attention", noting that pseudoscience may include "sightings of UFOs, alien abductions, astrology, psychic predictions ... [and] outlandish claims about the cause and cure of diseases".

Kalichman describes how quacks, like some of the academics involved, misrepresent their qualifications to create an illusion of authority. One, he claims, treats AIDS with hyperthermia, massage, oxygen, music, colour, gem, aroma, hypnosis, light and magnetic fields, each word followed by "therapy". Another allegedly distributed a product in Zambia called Tetrasil, a pesticide used in swimming pools, until the Zambian government intervened. Kalichman concludes that "taking money from the poor for bogus treatments is beyond criminal" and castigates journalist supporters of the denialist viewpoint for neglecting their professional obligations to verify facts and avoid sensationalist stories. In a powerful ending, Kalichman claims that extreme right-wing politics influences the AIDS denialist movement.

Professional institutions continue to tolerate the conduct of academic denialists, despite the suffering that has resulted. The standard excuse for inaction has been freedom of expression — the First Amendment of the United States Constitution. But free speech has recognized limits, and causing death is one. In 2006, as Kalichman records, a group of concerned scientists and activists created a website, AIDSTruth (http://www.aidstruth.org), to provide evidence to counter the denialists' words. The international legal and human-rights communities should now investigate the deadly impact of AIDS denialism. Action might have widespread benefits: Paul Offit's tour de force, Autism's False Prophets, claims that pseudoscientists and quacks have used similar tactics to parasitize the suffering of desperate parents by persuading them that vaccines cause autism. As Kalichman says, denialism "will not break until the public is educated to differentiate science from pseudoscience, facts from fraud".

John P. Moore is professor of microbiology and immunology at the Weill Medical College of Cornell University, New York 10021, USA.

Prof Moore's honorarium for this book review will be donated to the same charity that receives Seth Kalichman's royalties for the book – the Family Treatment Fund administered by the Massachusetts General Hospital and Harvard University.

'House of Numbers' is an AIDS denialist propaganda film

Eduard Grebe — Tue, 28 Apr 2009 14:37:06 +0000

by Jeanne Bergman

I went to Nashville to see the film House of Numbers, and it is indeed a piece of HIV denialist propaganda. The film maker presents himself as 1) an innocent young guy just looking for 2) the truth about HIV and AIDS but is increasingly confused by the seemingly contradictory things he learns, until he concludes that 3) poverty, not HIV, is the cause of deaths attributed to AIDS. 4) Much of his argument rests on the diagnostic protocols for both HIV and AIDS, and 5) the problem of effective, tolerable treatments. Finally, 6) it impugns the motives of both people with HIV and researchers, suggesting that they are all engaged in a hoax for money.

1) In fact, Brent Leung is not new to the topic: he has reportedly worked on videos (possibly never completed) based on books by two of the most bizarre AIDS theorists--in 1999, "Emerging Viruses" by Len Horowitz (anti-vaccine conspiracist) and in 2000, "State Origin" by Boyd Graves, who has a spread sheet he says proves that the federal government created HIV in its labs. Far from innocent, Leung misrepresented his denialist agenda to AIDS scientists and clinicians he interviewed.

2) Leung wasn't looking for the facts about HIV/AIDS; he was looking for footage that could support denialist theories and undermine public confidence in HIV science. He does this by editing footage so that HIV denialists look credible and scientists look grumpy, eccentric, or uncertain. (A few of them made this easy.) He juxtaposes brief clips from interviews with real scientists with one another and with people on the street, to create a false sense that on the one hand there is no scientific consensus about HIV , and on the other hand that a pharma conspiracy has misled ordinary people to think there is a consensus. He obscures the intense disagreements among denialists about whether HIV even exists, and he never states affirmatively his own conclusions, in that way ducking responsibility for the conclusions viewers are led to draw. (At Nashville, he said he was "neutral" on the question.) So for the record: not everything there is to know about HIV and AIDS was instantly known, and while there is an absolute scientific consensus that HIV is the necessary cause of AIDS, we are continuing to learn a lot about how the virus damages the immune system. Limits to scientific knowledge do not mean that what is being studied doesn't exist: it only means that science is a gradual process of theorizing, testing, and confirming.

3) Leung doesn't look at how different US populations most affected by AIDS (IV drug users, gay men, children of HIV+ women, low-income urban African-Americans, hemophiliacs) have only one thing in common: a virus that is transmitted by blood, semen and breast milk. The long-since disproven poppers theory is trotted out for KS and PCP in gay men, and then leung leaps to the African epidemic, to claim that the common denominator of communities affected by AIDS is poverty and malnutrition. He neglects to mention that the people who die from AIDS in Africa are primarily the strongest people in the prime of life who are most sexually active, not the elderly and very young who are the most vulnerable to malnutrition.

4) A lot of the film addresses seeming inconsistencies in HIV testing and AIDS diagnoses. First, it treats the gradual increase in knowledge, and therefore changes in definitions over time, as an indication that HIV isn't real and that political and profit motives drove the invention of the disease. Secondly, it treats the process of HIV screening (ELIZA antibody test plus interview) and confirmatory testing as if screens, false positives and confirming tests were an anomaly in medicine. They are not: they are routine and, used properly, essential. The variations in AIDS diagnoses in the US and Africa (where HIV tests may not be available) reflect environmental and economic differences between regions; the do not undermine the fact that an infectious pathogen, the virus called HIV, gradually destroys the immune system and allows opportunistic infections to take hold. Here is a basic fact: the existence of a deadly pathogen is independent of the language humans use to describe it and to diagnose the illness it causes.

5) The film attacks AZT a lot, emphasizing early problems with monotherapy and toxic dosages, and ignoring the effectiveness and relative ease of current ARV treatments. A few outlying cases are highlighted to imply that AIDS meds are always deadly and should not be prescribed. One is Joyce Ann Hafford, an HIV+ pregnant woman who was in a clinical trial for Combivir and nevirapine; her doctors apparently did not respond appropriately to signs of liver failure, and she died in 2004. This is a tragedy, but neither undermines the evidence that HIV exists nor the fact that millions are alive today because of ARVS (and watchful doctors). The second is Audrey Serrano, who apparently had one positive HIV antibody screen, and on this basis her doctor prescribed ARVs over several years. In fact, Serrano was not infected; the doctor committed malpractice by not confirming her HIV+ self-report and treating her without a proper, multistep diagnosis. She won a $2.5 million malpractice suit in 2007. And the third is a young woman, Lindsay Nagle, who was adopted from a Romanian orphanage. She tested negative for HIV antibodies there, but positive when she arrived in the US (along with parasites and other issues, according to her mother). A Western Blot was done, and the parents were told it was reactive--they didn't see it. The little girl was put on AZT and was in a lot of pain and did not thrive. In the film, the child's parents say that they reached out to denialist Peter Duesberg in dispair, who said to stop AZT immediately, and the child recovered. She is now 18. During the panel discussion in Nashville, it emerged that the Western Blot showed only two reactive bands and a viral load test was negative. So Lindsay was probably the victim of a bad diagnosis and was never HIV infected. AZT dosages in the early '90s were high, and the little girl was clearly harmed by a drug that is toxic at high levels. But her story, and her health today, do not disprove that HIV is the cause of AIDS: they merely prove that medical care in the US is uneven at best.

6) Throughout, the film implies that doctors, scientists, and people with HIV/AIDS are motivated by financial gain. In interview clips, young African-American men enumerate the benefits (reduced rent, home health aides, etc) they are entitled to with a diagnosis, implying that they aren't ill, just scamming. And because pharmaceutical corporations are profit-making businesses, the suggestion is that this disease was invented to make money when, in Peter Duesberg's explanation, a cancer virus wasn't found. But again, the fact that some corporations are making money does not mean that the virus, and the disease, don't exist.

I could go on and on, and I will, in a longer piece I am writing for AIDStruth.org. In the meantime, I urge everyone to be alert to the propaganda techniques that the film uses, and, if the film shows in your area (it is scheduled for Oklahoma in June), to be prepared to challenge the film's lies and help audiences understand the facts of HIV/AIDS.

NIAID: The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome

Nathan Geffen — Sat, 25 Apr 2009 11:24:24 +0000

(NIAID document written in 1995. Click here for version on NIAID site.)

Introduction

The acquired immunodeficiency syndrome (AIDS) is characterized by the progressive loss of the CD4+ helper/inducer subset of T lymphocytes, leading to severe immunosuppression and constitutional disease, neurological complications, and opportunistic infections and neoplasms that rarely occur in persons with intact immune function. Although the precise mechanisms leading to the destruction of the immune system have not been fully delineated, abundant epidemiologic, virologic and immunologic data support the conclusion that infection with the human immunodeficiency virus (HIV) is the underlying cause of AIDS.

The evidence for HIV's primary role in the pathogenesis of AIDS is reviewed elsewhere (Ho et al., 1987; Fauci, 1988, 1993a; Greene, 1993; Levy, 1993; Weiss, 1993). In addition, many scientists (Blattner et al., 1988a,b; Ginsberg, 1988; Evans, 1989a,b, 1992; Weiss and Jaffe, 1990; Gallo, 1991; Goudsmit, 1992; Groopman, 1992; Kurth, 1990; Ascher et al., 1993a,b; Schechter et al., 1993a,b; Lowenstein, 1994; Nicoll and Brown, 1994; Harris, 1995) have responded to specific arguments from individuals who assert that AIDS is not caused by HIV. The present discussion reviews the AIDS epidemic and summarizes the evidence supporting HIV as the cause of AIDS.

The Definition of AIDS

The term AIDS first appeared in the Morbidity and Mortality Weekly Report (MMWR) of the Centers for Disease Control (CDC) in 1982 to describe "... a disease, at least moderately predictive of a defect in cell-mediated immunity, occurring with no known cause for diminished resistance to that disease" (CDC, 1982b). The initial CDC list of AIDS-defining conditions, which included Kaposi's sarcoma (KS), Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC) and other conditions, has been updated on several occasions, with significant revisions (CDC, 1985a, 1987a, 1992a).

For surveillance purposes, the CDC currently defines AIDS in an adult or adolescent age 13 years or older as the presence of one of 25 AIDS-indicator conditions, such as KS, PCP or disseminated MAC. In children younger than 13 years, the definition of AIDS is similar to that in adolescents and adults, except that lymphoid interstitial pneumonitis and recurrent bacterial infections are included in the list of AIDS-defining conditions (CDC, 1987b). The case definition in adults and adolescents was expanded in 1993 to include HIV infection in an individual with a CD4+ T cell count less than 200 cells per cubic millimeter (mm3) of blood (CDC, 1992a). The current surveillance definition replaced criteria published in 1987 that were based on clinical conditions and evidence of HIV infection but not on CD4+ T cell determinations (CDC, 1987a).

In many developing countries, where diagnostic facilities may be minimal, epidemiologists employ a case definition based on the presence of various clinical symptoms associated with immune deficiency and the exclusion of other known causes of immunosuppression, such as cancer or malnutrition (Ryder and Mugewrwa, 1994a; Davachi, 1994).

The Designation AIDS is a Surveillance Tool

Surveillance definitions of AIDS have proven useful epidemiologically to track and quantify the recent epidemic of HIV-mediated immunosuppression and its manifestations. However, AIDS represents only the end stage of a continuous, progressive pathogenic process, beginning with primary infection with HIV, continuing with a chronic phase that is usually asymptomatic, leading to progressively severe symptoms and, ultimately, profound immunodeficiency and opportunistic infections and neoplasms (Fauci, 1993a). In clinical practice, symptomatology and measurements of immune function, notably levels of CD4+ T lymphocytes, are used to guide the treatment of HIV-infected persons rather than an all-or-nothing paradigm of AIDS/non-AIDS (CDC, 1992a; Sande et al., 1993; Volberding and Graham, 1994).

Quantifying the Epidemic

Between June 1981 and Dec. 31, 1994, 441,528 cases of AIDS in the United States, including 270,870 AIDS-related deaths, were reported to the CDC (CDC, 1995a). AIDS is now the leading cause of death among adults aged 25 to 44 in the United States (CDC, 1995b) (Figure 1).

Fig. 1. Death rates from leading causes of death in persons aged 25-44 years, United States, 1982-1993
Reference: Centers for Disease Control and Prevention

Worldwide, 1,025,073 cases of AIDS were reported to the World Health Organization (WHO) through December 1994, an increase of 20 percent since December 1993 (WHO, 1995a) (Figure 2). Allowing for under-diagnosis, incomplete reporting and reporting delay, and based on the available data on HIV infections around the world, the WHO estimates that over 4.5 million AIDS cumulative cases had occurred worldwide by late 1994 and that 19.5 million people worldwide had been infected with HIV since the beginning of the epidemic (WHO, 1995a). By the year 2000, the WHO estimates that 30 to 40 million people will have been infected with HIV and that 10 million people will have developed AIDS (WHO, 1994). The Global AIDS Policy Coalition has developed a considerably higher estimate--perhaps up to 110 million HIV infections and 25 million AIDS cases by the turn of the century (Mann et al., 1992a).

Fig. 2. Cumulative AIDS cases worldwide. AIDS cases reported to the World Health Organization through December 1994.
Reference: WHO, 1995a

A Brief History of the Emergence of AIDS

In 1981, clinical investigators in New York and California observed among young, previously healthy, homosexual men an unusual clustering of cases of rare diseases, notably Kaposi's sarcoma (KS) and opportunistic infections such as Pneumocystis carinii pneumonia (PCP), as well as cases of unexplained, persistent lymphadenopathy (CDC, 1981a,b, 1982a; Masur et al., 1981; Gottlieb et al., 1981; Friedman-Kien, 1981). It soon became evident that these men had a common immunologic deficit, an impairment in cell-mediated immunity resulting from a significant loss of "T-helper" cells, which bear the CD4 marker (Gottlieb et al., 1981; Masur et al., 1981; Siegal et al., 1981; Ammann et al., 1983a).

The widespread occurrence of KS and PCP in young people with no underlying disease or history of immunosuppressive therapy was unprecedented. Searches of the medical literature, autopsy records and tumor registries revealed that these diseases previously had occurred at very low levels in the United States (CDC, 1981b; CDC, 1982f).

KS, a very rare skin neoplasm, had affected mostly older men of Mediterranean origin or cancer or transplant patients undergoing immunosuppressive therapy (Gange and Jones, 1978; Safai and Good, 1981). Before the AIDS epidemic, the annual incidence of Kaposi's sarcoma in the United States was 0.02 to 0.06 per 100,000 population (Rothman, 1962a; Oettle, 1962). In addition, a more aggressive form of KS that generally occurred in younger individuals was seen in certain parts of Africa (Rothman, 1962b; Safai, 1984a). By 1984, never-married men in San Francisco were found to be 2,000 times more likely to develop KS than during the years 1973 to 1979 (Williams et al., 1994). As of Dec. 31, 1994, 36,693 patients with AIDS in the United States with a definitive diagnosis of KS had been reported to the CDC (CDC, 1995b).

PCP, a lung infection caused by a pathogen to which most individuals are exposed with no undue consequences, was extremely rare prior to 1981 in individuals other than those receiving immunosuppressive therapy or among the chronically malnourished, such as certain Eastern European children following World War II (Walzer, 1990). A 1967 survey, for example, found only 107 U.S. cases of PCP reported in the medical literature up to that point, virtually all among individuals with underlying immunosuppressive conditions or who had undergone immunosuppressive therapy (Le Clair, 1969). In that year, CDC became the sole supplier in the United States of pentamidine isethionate, then the only recommended PCP therapy, and began collecting data on each PCP case diagnosed and treated in this country. After reviewing requests for pentamidine in the period 1967 to 1970, researchers found only one case of confirmed PCP without a known underlying condition (Walzer et al., 1974). In the period immediately prior to the recognition of AIDS, January 1976 to June 1980, CDC received only one request for pentamidine isethionate to treat an adult in the United States who had PCP and no underlying disease (CDC, 1982f). In 1981 alone, 42 requests for pentamidine were received to treat patients with PCP and no known underlying disorders (CDC, 1982f). By Dec. 31, 1994, 127,626 individuals with AIDS in the United States with definitive diagnoses of PCP had been reported to the CDC (CDC, 1995b).

Another rare opportunistic disease, disseminated infection with the Mycobacterium avium complex (MAC), also was seen frequently in the first AIDS patients (Zakowski et al., 1982; Greene et al., 1982). Prior to 1981, only 32 individuals with disseminated MAC disease had been described in the medical literature (Masur, 1982a). By Dec. 31, 1994, the CDC had received reports of 28,954 U.S. AIDS patients with definitive diagnoses of disseminated MAC (CDC, 1995b).

Initial Theories

The fact that homosexual men constituted the initial population in which AIDS occurred in the United States led some to surmise that a homosexual lifestyle was specifically related to the disease (Goedert et al., 1982; Hurtenbach and Shearer, 1982; Sonnabend et al., 1983; Durack, 1981; Mavligit et al., 1984). These early suggestions that AIDS resulted from behavior specific to the homosexual population were largely dismissed when the syndrome was observed in distinctly different groups in the United States: in male and female injection drug users; in hemophiliacs and blood transfusion recipients; among female sex partners of bisexual men, recipients of blood or blood products, or injection drug users; and among infants born to mothers with AIDS or with a history of injection drug use (CDC, 1982b,c,d,f, 1983a; Poon et al., 1983; Elliot et al., 1983; Masur et al., 1982b; Davis et al., 1983; Harris et al., 1983; Rubinstein et al., 1983; Oleske et al., 1983; Ammann et al., 1983b). In 1983, for example, a study found that hemophiliacs with no history of any of the proposed causes of AIDS in homosexual men had developed the syndrome, and some of the men had apparently transmitted the infection to their wives (deShazo et al., 1983).

Many public health experts concluded that the clustering of AIDS cases (Auerbach et al., 1984; Gazzard et al., 1984) and the occurrence of cases in diverse risk groups could be explained only if AIDS were caused by an infectious microorganism transmitted in the manner of hepatitis B virus (HBV): by sexual contact, by inoculation with blood or blood products, and from mother to newborn infant (Francis et al., 1983; Curran et al., 1984; AMA, 1984; CDC, 1982f, 1983a,b).

Early suspects for the cause of AIDS were cytomegalovirus (CMV), because of its association with immunosuppression, and Epstein-Barr virus (EBV), which has an affinity for lymphocytes (Gottlieb et al., 1981; Hymes et al., 1981; CDC, 1982f). However, AIDS was a new phenomenon, and these viruses already had a worldwide distribution. Comparative seroprevalence studies showed no convincing evidence to assign these viruses or other known agents a primary role in the syndrome (Rogers et al., 1983). Also lacking was evidence that these viruses, when isolated from patients with AIDS, differed significantly from strains found in healthy individuals or from strains found in the years preceding the emergence of AIDS (AMA, 1984).

Retrovirus Hypothesis

By 1983, several research groups had focused on retroviruses for clues to the cause of AIDS (Gallo and Montagnier, 1987). Two recently recognized retroviruses, HTLV-I and HTLV-II, were the only viruses then known to preferentially infect helper T lymphocytes, the cells depleted in people with AIDS (Gallo and Reitz, 1982; Popovic et al., 1984). The pattern of HTLV transmission was similar to that seen among AIDS patients: HTLV was transmitted by sexual contact, from mother to child or by exposure to infected blood (Essex, 1982; Gallo and Reitz, 1982). In addition, HTLV-I was known to cause mild immunosuppression, and a related retrovirus, the lymphotropic feline leukemia virus (FeLV), caused lethal immunosuppression in cats (Essex et al., 1975).

In May 1983, the first report providing experimental evidence for an association between a retrovirus and AIDS was published (Barre-Sinoussi et al., 1983). After finding antibodies cross-reactive with HTLV-I in a homosexual patient with lymphadenopathy, a group led by Dr. Luc Montagnier isolated a previously unrecognized virus containing reverse transcriptase that was cytopathic for cord-blood lymphocytes (Barre-Sinoussi et al., 1983). This virus later became known as lymphadenopathy-associated virus (LAV). The French group subsequently reported that LAV was tropic for T-helper cells, in which it grew to substantial titers and caused cell death (Klatzmann et al., 1984a; Montagnier et al., 1984).

In 1984, a considerable amount of new data added to the evidence for a retroviral etiology for AIDS. Researchers at the National Institutes of Health reported the isolation of a cytopathic T-lymphotropic virus from 48 different people, including 18 of 21 with pre-AIDS, three of four clinically normal mothers of children with AIDS, 26 of 72 children and adults with AIDS, and one (who later developed AIDS) of 22 healthy homosexuals (Gallo et al., 1984). The virus, named HTLV-III, could not be found in 115 healthy heterosexual subjects.

Antibodies reactive with HTLV-III antigens were found in serum samples of 88 percent of 48 patients with AIDS, 79 percent of 14 homosexuals with pre-AIDS, and fewer than 1 percent of hundreds of healthy heterosexuals (Sarngadharan et al., 1984).

Shortly thereafter, the researchers found that 100 percent (34 of 34) of AIDS patients tested were positive for HTLV-III antibodies in a study in which none of 14 controls had antibodies (Safai et al., 1984b).

In a study in the United Kingdom reported later that year, investigators found that 30 of 31 AIDS patients tested were seropositive for HTLV-III antibodies, as were 110 of 124 individuals with persistent generalized lymphadenopathy (Cheingsong-Popov et al., 1984). None of more than 1,000 blood donors selected randomly had antibodies to HTLV-III in this study.

During the same time period, HTLV-III was isolated from the semen of patients with AIDS (Zagury et al., 1984, Ho et al., 1984), findings consistent with the epidemiologic data demonstrating AIDS transmission via sexual contact.

Researchers in San Francisco subsequently reported the isolation of a retrovirus they named the AIDS-associated retrovirus (ARV) from AIDS patients in different risk groups, as well as from asymptomatic people from AIDS risk groups (Levy et al., 1984). The researchers isolated ARV from 27 of 55 patients with AIDS or lymphadenopathy syndrome; they detected antibodies to ARV in 90 percent of 113 individuals with the same conditions. Like HTLV-III and LAV, ARV grew substantially in peripheral blood mononuclear cells and killed CD4+ T cells. The same group subsequently isolated ARV from genital secretions of women with antibodies to the virus, data consistent with the observation that men could contract AIDS following contact with a woman infected with the virus (Wofsy et al., 1986).

During the same period, HTLV-III and ARV were isolated from the brains of children and adults with AIDS-associated encephalopathy, which suggested a role for these viruses in the central nervous system disorders seen in many patients with AIDS (Levy et al., 1985; Ho et al., 1985).

By 1985, analyses of the nucleotide sequences of HTLV-III, LAV and ARV demonstrated that the three viruses belonged to the same retroviral family and were strikingly similar (Wain-Hobson et al., 1985; Ratner et al., 1985; Sanchez-Pescador et al., 1985). In 1986, the International Committee of Viral Taxonomy renamed the viruses the human immunodeficiency virus (HIV) (Coffin et al., 1986).

Seroprevalence Surveys

Serologic tests for antibodies to HIV, developed in 1984 (Sarngadharan et al., 1984; Popovic et al., 1984; reviewed in Brookmeyer and Gail, 1994), have enabled researchers to conduct hundreds of seroprevalence surveys throughout the world. Using these tests, investigators have repeatedly demonstrated that the occurrence of AIDS-like illnesses in different populations has closely followed the appearance of HIV antibodies (U.S. Bureau of the Census, 1994). For example, retrospective examination of sera collected in the late 1970s in association with hepatitis B studies in New York, San Francisco and Los Angeles suggests that HIV entered the U.S. population sometime in the late 1970s (Jaffe et al., 1985a). In 1978, 4.5 percent of men in the San Francisco cohort had antibodies to HIV (Jaffe et al., 1985a). The first cases of AIDS in homosexual men in San Francisco were reported in 1981, and by 1984, more than two-thirds of the San Francisco cohort had HIV antibodies and almost one-third had developed AIDS-related conditions (Jaffe et al., 1985a). By the end of 1992, approximately 70 percent of 539 men in the San Francisco cohort with a well-documented date of HIV seroconversion before 1983 had developed an AIDS-defining condition or had a CD4+ T cell count of less than 200/mm3; another 11 percent had CD4+ T cell counts between 200 and 500/mm3 (Buchbinder et al., 1994) (Figure 3).

Fig. 3. Clinical and imunologic outcomes in patients HIV-infected for 10-15 years in the San Francisco City Clinic; n=539.
Modified from Buchbinder et al., 1994.

Retrospective tests of the U.S. blood supply have shown that, in 1978, at least one batch of Factor VIII was contaminated with HIV (Evatt et al., 1985; Aronson, 1993). Factor VIII was given to some 2,300 males in the United States that year. In July 1982, the first cases of AIDS in hemophiliacs were reported (CDC, 1982c). Through Dec. 31, 1994, 3,863 individuals in the United States with hemophilia or other coagulation disorders had been diagnosed with AIDS (CDC, 1995a).

Elsewhere in the world, a similar chronological association between HIV and AIDS has been noted. The appearance of HIV in the blood supply has preceded or coincided with the occurrence of AIDS cases in every country and region where cases of AIDS have been reported (Institute of Medicine, 1986; Chin and Mann, 1988; Curran et al., 1988; Piot et al., 1988; Mann, 1992; Mann et al., 1992; U.S. Bureau of the Census, 1994). For example, a review of serosurveys associated with dengue fever in the Caribbean found that the earliest evidence of HIV infection in Haiti appeared in samples from 1979 (Pape et al., 1983, 1993); the first cases of AIDS in Haiti and in Haitians in the United States were reported in the early 1980s (CDC, 1982e; Pape et al., 1983, 1993).

In Africa between 1981 and 1983, clinical epidemics of chronic, life-threatening enteropathic diseases ("slim disease"), cryptococcal meningitis, progressive KS and esophageal candidiasis were recognized in Rwanda, Tanzania, Uganda, Zaire and Zambia, and in 1983 the first AIDS cases among Africans were reported (Quinn et al., 1986; Essex, 1994). The earliest blood sample from Africa from which HIV has been recovered is from a possible AIDS patient in Zaire, tested in connection with a 1976 Ebola virus outbreak (Getchell et al., 1987; Myers et al., 1992).

Serologic data have suggested the presence of HIV infection as early as 1959 in Zaire (Nahmias et al., 1986). Other investigators have found evidence of HIV proviral DNA in tissues of a sailor who died in Manchester, England, in 1959 (Corbitt et al., 1990). In the latter case, this finding may have represented a contamination with a virus isolated at a much later date (Zhu and Ho, 1995).

HIV did not become epidemic until 20 to 30 years later, perhaps because of the migration of poor and young sexually active individuals from rural areas to urban centers in developing countries, with subsequent return migration and, internationally, due to civil wars, tourism, business travel and the drug trade (Quinn, 1994).

HIV and Other Lentiviruses

As a retrovirus, HIV is an RNA virus that codes for the enzyme reverse transcriptase, which transcribes the viral genomic RNA into a DNA copy that ultimately integrates into the host cell genome (Fauci, 1988). Within the retrovirus family, HIV is classified as a lentivirus, having genetic and morphologic similarities to animal lentiviruses such as those infecting cats (feline immunodeficiency virus), sheep (visna virus), goats (caprine arthritis-encephalitis virus), and non-human primates (simian immunodeficiency virus) (Stowring et al., 1979; Gonda et al., 1985; Haase, 1986; Temin, 1988, 1989). Like HIV in humans, these animal viruses primarily infect cells of the immune system, including T lymphocytes and macrophages (Haase, 1986, 1990; Levy, 1993) (Table 1).

Table 1. Lentiviruses

Virus	Host	Primary cell type	Clinical disorder
Equine infectious anemia virus (EIAV)	Horse	Macrophages	Cyclical infection in the first year: hemolytic anemia and sometimes encephalopathy
Visna virus	Sheep	Macrophages	Encephalopathy
Caprine arthritisencephalitis virus (CAEV)	Goat	Macrophages	Immune deficiency, encephalopathy
Bovine immune deficiency virus (BIV)	Cow	Macrophages	Lymphadenopathy, lymphocytosis, CNS disease (?)
Feline immunodeficiency virus (FIV)	Cat	T lymphocytes	Immune deficiency
Simian immunodeficiency (SIV)	Primate	T lymphocytes	Immune deficiency, encephalopathy
Humanimmunodeficiency virus (HIV)	Human	T lymphocytes	Immune deficiency, encephalopathy

Reference: Levy, 1993.

Lentiviruses often cause immunodeficiency in their hosts in addition to slow, progressive wasting disorders, neurodegeneration and death (Haase, 1986, 1990). SIV, for example, infects several subspecies of macaque monkeys, causing diarrhea, wasting, CD4+ T cell depletion, opportunistic infections and death (Desrosiers, 1990; Fultz, 1993). HIV is closely related to SIV, as evidenced by viral protein cross-reactivity and genetic sequence similarities (Franchini et al., 1987; Hirsch et al., 1989; Desrosiers, 1990; Myers, 1992).

One feature that distinguishes lentiviruses from other retroviruses is the remarkable complexity of their viral genomes. Most retroviruses that are capable of replication contain only three genes--env, gag and pol (Varmus, 1988). HIV contains not only these essential genes but also the complex regulatory genes tat, rev, nef, and auxiliary genes vif, vpr and vpu (Greene, 1991). The actions of these additional genes probably contribute to the profound pathogenicity that differentiates HIV from many other retroviruses.

CD4+ T cells, the cells depleted in AIDS patients, are primary targets of HIV because of the affinity of the gp120 glycoprotein component of the viral envelope for the CD4 molecule (Dalgleish et al., 1984; Klatzmann et al., 1984b; McDougal et al., 1985a, 1986). These so-called T-helper cells coordinate a number of critical immunologic functions. The loss of these cells results in the progressive impairment of the immune system and is associated with a deteriorating clinical course (Pantaleo et al., 1993a). In advanced HIV disease, abnormalities of virtually every component of the immune system are evident (Fauci, 1993a; Pantaleo et al., 1993a).

Course of HIV Infection

Primary HIV infection is associated with a burst of HIV viremia and often a concomitant abrupt decline of CD4+ T cells in the peripheral blood (Cooper et al., 1985; Daar et al., 1991; Tindall and Cooper, 1991; Clark et al., 1991; Pantaleo et al., 1993a, 1994). The decrease in circulating CD4+ T cells during primary infection is probably due both to HIV-mediated cell killing and to re-trafficking of cells to the lymphoid tissues and other organs (Fauci, 1993a).

The median period of time between infection with HIV and the onset of clinically apparent disease is approximately 10 years in western countries, according to prospective studies of homosexual men in which dates of seroconversion are known (Lemp et al., 1990; Pantaleo et al., 1993a; Hessol et al., 1994) (Figure 4). Similar estimates of asymptomatic periods have been made for HIV-infected blood-transfusion recipients, injection drug users and adult hemophiliacs (reviewed in Alcabes et al., 1993a).

Fig. 4. Typical course of HIV infection. During the period following primary infection, HIV disseminates widely in the body; an abrupt decrease in CD4+ T cells in the peripheral circulation is often seen. An immune response to HIV ensures, with a decrease in detectable viremia. A period of clinical latency follows, during which CD4+ T cells counts continue to decrease, until they fall to a critical level below which there is a substantial risk of opportunistic infections.
Adapted from Pantaleo et al., 1993a

HIV disease, however, is not uniformly expressed in all individuals. A small proportion of persons infected with the virus develop AIDS and die within months following primary infection, while approximately 5 percent of HIV-infected individuals exhibit no signs of disease progression even after 12 or more years (Pantaleo et al., 1995a; Cao et al., 1995). Host factors such as age or genetic differences among individuals, the level of virulence of the individual strain of virus, as well as influences such as co-infection with other microbes may determine the rate and severity of HIV disease expression in different people (Fauci, 1993a; Pantaleo et al., 1993a). Such variables have been termed "clinical illness promotion factors" or co-factors and appear to influence the onset of clinical disease among those infected with any pathogen (Evans, 1982). Most people infected with hepatitis B, for example, show no symptoms or only jaundice and clear their infection, while others suffer disease ranging from chronic liver inflammation to cirrhosis and hepatocellular carcinoma (Robinson, 1990). Co-factors probably also determine why some smokers develop lung cancer, while others do not.

As disease progresses, increasing amounts of infectious virus, viral antigens and HIV-specific nucleic acids in the body correlate with a worsening clinical course (Allain et al., 1987; Nicholson et al., 1989; Ho et al., 1989; Schnittman et al., 1989, 1990a, 1991; Mathez et al., 1990; Genesca et al., 1990; Hufert et al., 1991; Saag et al., 1991; Aoki-Sei et al., 1992; Yerly et al., 1992; Bagnarelli et al., 1992; Ferre et al., 1992; Michael et al., 1992; Pantaleo et al., 1993b; Gupta et al., 1993; Connor et al., 1993; Saksela et al., 1994; Dickover et al., 1994; Daar et al., 1995; Furtado et al., 1995).

Cross-sectional studies in adults and children have shown that levels of infectious HIV or proviral DNA in the blood are substantially higher in patients with AIDS than in asymptomatic patients (Ho et al., 1989; Coombs et al., 1989; Saag et al., 1991; Srugo et al., 1991; Michael et al., 1992; Aoki-Sei et al., 1992). In both blood and lymph tissues from HIV-infected individuals, researchers at the National Institutes of Health found viral burden and replication to be substantially higher in patients with AIDS than in early-stage patients (Pantaleo et al., 1993b). This group also found deterioration of the architecture and microenvironment of the lymphoid tissue to a greater extent in late-stage patients than in asymptomatic individuals. The dissolution of the follicular dendritic cell network of the lymph node germinal center and the progressive loss of antigen-presenting capacity are likely critical factors that contribute to the immune deficiency seen in individuals with AIDS (Pantaleo et al., 1993b).

More recently, the same group studied 15 long-term non-progressors, defined as individuals infected for more than seven years (usually more than 10 years) who received no antiretroviral therapy and showed no decline in CD4+ T cells. They found that viral burden and viral replication in the peripheral blood and in lymph nodes, measured by DNA and RNA PCR, respectively, were at least 10 times lower than in 18 HIV-infected individuals whose disease progression was more typical. In addition, the lymph node architecture in long-term non-progressors remained intact (Pantaleo et al., 1995a).

Longitudinal studies also have quantified viral burden and replication in the blood and their relationship to disease progression (Schnittman et al., 1990a; Connor et al., 1993; Saksela et al., 1994; Daar et al., 1995; Furtado et al., 1995). In a study of asymptomatic HIV-infected individuals who ultimately developed rapidly progressive disease, the number of CD4+ T cells in which HIV DNA could be found increased over time, whereas this did not occur in patients with stable disease (Schnittman et al., 1990a). Using serial blood samples from HIV-infected individuals who had a precipitous drop in CD4+ T cells followed by a rapid progression to AIDS, other groups found a significant increase in the levels of HIV DNA concurrent with or prior to CD4+ T cell decline (Connor et al., 1993; Daar et al., 1995). Increased expression of HIV mRNA in peripheral blood mononuclear cells has also been shown to precede clinically defined progression of disease (Saksela et al., 1994).

In the longitudinal Multicenter AIDS Cohort Study (MACS), homosexual and bisexual men for whom the time of seroconversion had been documented had increasing levels of both plasma HIV RNA and intracellular RNA as disease progressed and had CD4+ T cell numbers that declined (Gupta et al., 1993; Mellors et al., 1995). Men who remained asymptomatic with stable CD4+ T cell numbers maintained extremely low levels of viral RNA. These findings suggest that plasma HIV RNA levels are a strong, CD4-independent predictor of rapid progression to AIDS. Another longitudinal study found that increasing plasma RNA levels were highly predictive of the development of zidovudine (AZT) resistance and death in patients on long-term therapy with that drug (Vahey et al., 1994).

Other evidence suggests that changes in viral load due to changes in therapy can predict clinical benefit in patients. It was recently found that the amount of HIV RNA in the peripheral blood decreased in patients who switched to didanosine (ddI) after taking AZT and increased in patients who continued to take AZT (NTIS, 1994; Welles et al., 1995). Decreases in HIV RNA were associated with fewer progressions to new, previously undiagnosed AIDS-defining diseases or death. This study provided the first evidence that a therapy-induced reduction of HIV viral load is associated with clinical outcome. Similarly, studies of blood samples collected serially from HIV-infected patients found that a decrease in HIV RNA copy number in the first months following treatment with AZT strongly correlated with improved clinical outcome (O'Brien et al., 1994; Jurriaans et al., 1995).

The emergence of HIV variants that are more cytopathic and replicate in a wider range of susceptible cells in vitro has also been shown to correlate with disease progression in HIV-infected individuals (Fenyo et al., 1988; Tersmette et al., 1988, 1989a,b; Richman and Bozzette, 1994; Connor et al., 1993, Connor and Ho, 1994a,b). Similar results have been seen in vivo with macaques infected with molecularly cloned SIV (Kodama et al., 1993). It has also been reported that HIV isolates from patients who progress to AIDS have a higher rate of replication compared with HIV isolates from individuals who remain asymptomatic (Fenyo et al., 1988; Tersmette et al., 1989a), and that rapidly replicating variants of HIV emerge during the asymptomatic stage of infection prior to disease progression (Tersmette et al., 1989b; Connor and Ho, 1994b).

Immunologic Profile of People With AIDS

It is well established that a number of viral, rickettsial, fungal, protozoal and bacterial infections can cause transient T cell decreases (Chandra, 1983). Immune deficiencies due to tumors, autoimmune diseases, rare congenital disorders, chemotherapy and other factors have been shown to render certain individuals susceptible to opportunistic infections (Ammann, 1991). As mentioned above, chronic malnutrition following World War II resulted in PCP in Eastern European children (Walzer, 1990). Transplant recipients treated with immunosuppressive drugs such as cyclosporin and glucocorticoids often suffer recurrent diseases due to pathogens such as varicella zoster virus and cytomegalovirus that also cause disease in HIV-infected individuals (Chandra, 1983; Ammann, 1991).

However, the specific immunologic profile that typifies AIDS--a progressive reduction of CD4+ T cells resulting in persistent CD4+ T lymphocytopenia and profound deficits in cellular immunity--is extraordinarily rare in the absence of HIV infection or other known causes of immunosuppression. This was recently demonstrated in several surveys that sought to determine the frequency of idiopathic CD4+ T-cell lymphocytopenia (ICL), which is characterized by CD4+ T cell counts lower than 300 cells per cubic millimeter (mm3) of blood in the absence of HIV antibodies or conditions or therapies associated with depressed levels of CD4+ T cells (reviewed in Fauci, 1993b; Laurence, 1993).

In a CDC survey, only 47 (.02 percent) of 230,179 individuals diagnosed with AIDS were both HIV-seronegative and had persistently low CD4+ T cell counts (<300/MM3) in the absence of conditions or therapies associated with immunosuppression (Smith et al., 1993).

In the MACS, 22,643 CD4+ T cell determinations in 2,713 HIV-seronegative homosexual men revealed only one individual with a CD4+ T cell count persistently lower than 300 cells/mm3, and this individual was receiving immunosuppressive therapy (Vermund et al., 1993a). A similar review of another cohort of homosexual and bisexual men found no case of persistently lowered CD4+ T cell counts among 756 HIV-seronegative men who had no other cause of immunosuppression (Smith et al., 1993). Analogous results were reported from the San Francisco Men's Health Study, a population-based cohort recruited in 1984. Among 206 HIV-seronegative heterosexual and 526 HIV-seronegative homosexual or bisexual men, only one had consistently low CD4+ T cell counts (Sheppard et al., 1993). This individual also had low CD8+ T cell counts, suggesting that he had general lymphopenia rather than a selective loss of CD4+ T cells. No AIDS-defining clinical condition was observed among these HIV-seronegative men.

Studies of blood donors, recipients of blood and blood products, and household and sexual contacts of transfusion recipients also suggest that persistently low CD4+ T cell counts are extremely rare in the absence of HIV infection (Aledort et al., 1993; Busch et al., 1994). Longitudinal studies of injection-drug users have demonstrated that unexplained CD4+ T lymphocytopenia is almost never seen among HIV-seronegative individuals in this population, despite a high risk of exposure to hepatitis B, cytomegalovirus and other blood-borne pathogens (Des Jarlais et al., 1993; Weiss et al., 1992).

Mechanisms of CD4+ T Cell Depletion

HIV infects and kills CD4+ T lymphocytes in vitro, although scientists have developed immortalized T-cell lines in order to propagate HIV in the laboratory (Popovic et al., 1984; Zagury et al., 1986; Garry, 1989; Clark et al., 1991). Several mechanisms of CD4+ T cell killing have been observed in lentivirus systems in vitro and may explain the progressive loss of these cells in HIV-infected individuals (reviewed in Garry, 1989; Fauci, 1993a; Pantaleo et al., 1993a) (Table 2). These mechanisms include disruption of the cell membrane as HIV buds from the surface (Leonard et al., 1988) or the intracellular accumulation of heterodisperse RNAs and unintegrated DNA (Pauza et al., 1990; Koga et al., 1988). Evidence also suggests that intracellular complexing of CD4 and viral envelope products can result in cell killing (Hoxie et al., 1986).

Table 2. Potential Mechanisms of the Functional and Quantitative Depletion of CD4 T Lymphocytes

Direct HIV-mediated cytopathic effects (single-cell killing)

HIV-mediated formation of syncytia

Virus-specific immune responses

HIV-specific cytolytic T lymphocytes

Antibody-dependent cellular cytotoxicity

Natural killer cells

Autoimmune mechanisms

Anergy caused by inappropriate cell signaling through gp120-CD4 interaction

Superantigen-mediated perturbation of T-cell subgroups

Programmed cell death (apoptosis)

Reference: Pantaleo et al., 1993a.

In addition to these direct mechanisms of CD4+ T cell depletion, indirect mechanisms may result in the death of uninfected CD4+ T cells (reviewed in Fauci, 1993a; Pantaleo et al., 1993a). Uninfected cells often fuse with infected cells, resulting in giant cells called syncytia that have been associated with the cytopathic effect of HIV in vitro (Sodroski et al., 1986; Lifson et al., 1986). Uninfected cells also may be killed when free gp120, the envelope protein of HIV, binds to their surfaces, marking them for destruction by antibody-dependent cellular cytotoxicity responses (Lyerly et al., 1987). Other autoimmune phenomena may also contribute to CD4+ T cell death since HIV envelope proteins share some degree of homology with certain major histocompatibility complex type II (MHC-II) molecules (Golding et al., 1989; Koenig et al., 1988).

A number of investigators have suggested that superantigens, either encoded by HIV or derived from unrelated agents, may trigger massive stimulation and expansion of CD4+ T cells, ultimately leading to depletion or anergy of these cells (Janeway, 1991; Hugin et al., 1991). The untimely induction of a form of programmed cell death called apoptosis has been proposed as an additional mechanism for CD4+ T cell loss in HIV infection (Ameisen and Capron, 1991; Terai et al., 1991; Laurent-Crawford et al., 1991). Recent reports indicate that apoptosis occurs to a greater extent in HIV-infected individuals than in non-infected persons, both in the peripheral blood and lymph nodes (Finkel et al., 1995; Pantaleo and Fauci, 1995b; Muro-Cacho et al., 1995).

It has also been observed that HIV infects precursors of CD4+ T cells in the bone marrow and thymus and damages the microenvironment of these organs necessary for the optimal sustenance and maturation of progenitor cells (Schnittman et al., 1990b; Stanley et al., 1992). These findings may help explain the lack of regeneration of the CD4+ T cell pool in patients with AIDS (Fauci, 1993a).

Recent studies have demonstrated a substantial viral burden and active viral replication in both the peripheral blood and lymphoid tissues even early in HIV infection (Fox et al., 1989; Coombs et al., 1989; Ho et al., 1989; Michael et al., 1992; Bagnarelli et al., 1992; Pantaleo et al., 1993b; Embretson et al., 1993; Piatak et al., 1993). One group has reported that 25 percent of CD4+ T cells in the lymph nodes of HIV-infected individuals harbor HIV DNA early in the course of disease (Embretson et al., 1993). Other data suggest that HIV infection is sustained by a dynamic process involving continuous rounds of new viral infection and the destruction and replacement of over 1 billion CD4+ T cells per day (Wei et al., 1995; Ho et al., 1995).

Taken together, these studies strongly suggest that HIV has a central role in the pathogenesis of AIDS, either directly or indirectly by triggering a series of pathogenic events that contribute to progressive immunosuppression.

Koch's Postulates Fulfilled

Recent developments in HIV research provide some of the strongest evidence for the causative role of HIV in AIDS and fulfill the classical postulates for disease causation developed by Henle and Koch in the 19th century (Koch's postulates reviewed in Evans, 1976, 1989a; Harden, 1992). Koch's postulates have been variously interpreted by many scientists over the years. One scientist who asserts that HIV does not cause AIDS has set forth the following interpretation of the postulates for proving the causal relationship between a microorganism and a specific disease (Duesberg, 1987):

The microorganism must be found in all cases of the disease.
It must be isolated from the host and grown in pure culture.
It must reproduce the original disease when introduced into a susceptible host.
It must be found in the experimental host so infected.
Recent developments in HIV/AIDS research have shown that HIV fulfills these criteria as the cause of AIDS.

1) The development of DNA PCR has enabled researchers to document the presence of cell-associated proviral HIV in virtually all patients with AIDS, as well as in individuals in earlier stages of HIV disease (Kwok et al., 1987; Wages et al., 1991; Bagasra et al., 1992; Bruisten et al., 1992; Petru et al., 1992; Hammer et al., 1993). RNA PCR has been used to detect cell-free and/or cell-associated viral RNA in patients at all stages of HIV disease (Ottmann et al., 1991; Schnittman et al., 1991; Aoki-Sei, 1992; Michael et al., 1992; Piatak et al., 1993) (Table 3).

Table 3. Assays to Detect/Measure HIV Antibody-Positive Patients

Assay	% of antibodypositivepatients	CD4+ range(cells/mm3)	Viral parameter measured
p24antigen	20 37-95	200-500 < 200	Free viral antigen in serum orplasma
ICD p24	45-70 75-100	200-500 < 200	Immune-complexed viral antigenin serum or plasma
Plasmaviremia)	75-100	< 200	Infectious cell-free virus
PBMCculture	95-100	< 500	Infectious cell-associated andamplifiable virus
DNA PCR	100	< 1,000	Cell-associated proviral DNA
RNA PCR	100	< 1,000	Cell-free and/or cell-associatedviral RNA

Modified from Hammer et al., 1993.

2) Improvements in co-culture techniques have allowed the isolation of HIV in virtually all AIDS patients, as well as in almost all seropositive individuals with both early- and late-stage disease (Coombs et al., 1989; Schnittman et al., 1989; Ho et al., 1989; Jackson et al., 1990).

1-4) All four postulates have been fulfilled in three laboratory workers with no other risk factors who have developed AIDS or severe immunosuppression after accidental exposure to concentrated HIVIIIB in the laboratory (Blattner et al., 1993; Reitz et al., 1994; Cohen, 1994c). Two patients were infected in 1985 and one in 1991. All three have shown marked CD4+ T cell depletion, and two have CD4+ T cell counts that have dropped below 200/mm3 of blood. One of these latter individuals developed PCP, an AIDS indicator disease, 68 months after showing evidence of infection and did not receive antiretroviral drugs until 83 months after the infection. In all three cases, HIVIIIB was isolated from the infected individual, sequenced, and shown to be the original infecting strain of virus.

In addition, as of Dec. 31, 1994, CDC had received reports of 42 health care workers in the United States with documented, occupationally acquired HIV infection, of whom 17 have developed AIDS in the absence of other risk factors (CDC, 1995a). These individuals all had evidence of HIV seroconversion following a discrete percutaneous or mucocutaneous exposure to blood, body fluids or other clinical laboratory specimens containing HIV.

The development of AIDS following known HIV seroconversion also has been repeatedly observed in pediatric and adult blood transfusion cases (Ward et al., 1989; Ashton et al., 1994), in mother-to-child transmission (European Collaborative Study, 1991, 1992; Turner et al., 1993; Blanche et al., 1994), and in studies of hemophilia, injection drug use, and sexual transmission in which the time of seroconversion can be documented using serial blood samples (Goedert et al., 1989; Rezza et al., 1989; Biggar, 1990; Alcabes et al., 1993a,b; Giesecke et al., 1990; Buchbinder et al., 1994; Sabin et al., 1993).

In many such cases, infection is followed by an acute retroviral syndrome, which further strengthens the chronological association between HIV and AIDS (Pedersen et al., 1989, 1993; Schechter et al., 1990; Tindall and Cooper, 1991; Keet et al., 1993; Sinicco et al., 1993; Bachmeyer et al., 1993; Lindback et al., 1994).

Evidence From Animal and Laboratory Models

A recent study demonstrated that an HIV variant that causes AIDS in humans--HIV-2--also causes a similar syndrome when injected into baboons (Barnett et al., 1994). Over the course of two years, HIV-2-infected animals exhibited a significant decline in immune function, as well as lymphocytic interstitial pneumonia (which often afflicts children with AIDS), the development of lesions similar to those seen in Kaposi's sarcoma, and severe weight loss akin to the wasting syndrome that occurs in human AIDS patients. Other studies suggest that pigtailed macaques also develop AIDS-associated diseases subsequent to HIV-2 infection (Morton et al., 1994).

Asian monkeys infected with clones of the simian immunodeficiency virus (SIV), a lentivirus closely related to HIV, also develop AIDS-like syndromes (reviewed in Desrosiers, 1990; Fultz, 1993). In macaque species, various cloned SIV isolates induce syndromes that parallel HIV infection and AIDS in humans, including early lymphadenopathy and the occurrence of opportunistic infections such as pulmonary Pneumocystis carinii infection, cytomegalovirus, cryptosporidium, candida and disseminated MAC (Letvin et al., 1985; Kestler et al., 1990; Dewhurst et al., 1990; Kodama et al., 1993).

In cell culture experiments, molecular clones of HIV are tropic for the same cells as clinical HIV isolates and laboratory strains of the virus and show the same pattern of cell killing (Hays et al., 1992), providing further evidence that HIV is responsible for the immune defects of AIDS. Moreover, in severe combined immunodeficiency (SCID) mice with human thymus/liver implants, molecular clones of HIV produce the same patterns of cell killing and pathogenesis as seen with clinical isolates (Bonyhadi et al., 1993; Aldrovandi et al., 1993).

Geographic Considerations

Convincing evidence that HIV causes AIDS also comes from the geographic correlation between rates of HIV antibody positivity and incidence of disease. Numerous studies have shown that AIDS is common only in populations with a high seroprevalence of HIV antibodies. Conversely, in populations in which HIV antibody seroprevalence is low, AIDS is extremely rare (U.S. Bureau of the Census, 1994).

Malawi, a country in southern Africa with 8.2 million inhabitants, reported 34,167 cases of AIDS to the WHO as of December 1994 (WHO, 1995a). This is the highest case rate in the region. The rate of HIV seroprevalence in Malawi is also high, as evidenced by serosurveys of pregnant women and blood donors (U.S. Bureau of the Census, 1994). In one survey, approximately 23 percent of more than 6,600 pregnant women in urban areas were HIV-positive (Dallabetta et al., 1993). Approximately 20 percent of 547 blood donors in a 1990 survey were HIV-positive (Kool et al., 1990).

In contrast, Madagascar, an island country off the southeast coast of Africa with a population of 11.3 million, reported only nine cases of AIDS to the WHO through December 1994 (WHO, 1995a). HIV seroprevalence is extremely low in this country; in recent surveys of 1,629 blood donors and 1,111 pregnant women, no evidence of HIV infection was found (Rasamindrakotroka et al., 1991). Yet, other sexually transmitted diseases are common in Madagascar; a 1989 seroepidemiologic study for syphilis found that 19.5 percent of 12,457 persons tested were infected (Latif, 1994; Harms et al., 1994). It is likely that due to the relative geographic isolation of this island nation, HIV was introduced late into its population. However, the high rate of other STDs such as syphilis would predict that HIV will spread in this country in the future.

Similar patterns have been noted in Asia. Thailand reported 13,246 cases of AIDS to the WHO through December 1994, up from only 14 cases through 1988 (WHO, 1995a) (Figure 5). This rise has paralleled the spread of HIV infection in Thailand. Through 1987, fewer than .05 percent of 200,000 Thais from all risk groups were HIV-seropositive (Weniger et al., 1991). By 1993, 3.7 percent of 55,000 inductees into the Royal Thai Army tested positive for HIV antibodies, up from 0.5 percent of men recruited in 1989 (U.S. Bureau of the Census Database, December 1994). Seropositivity among brothel prostitutes in Thailand rose from 3.5 percent in June 1989 to 27.1 percent in June 1993 (Hanenberg et al., 1994). By mid-1993, an estimated 740,00 people were infected with HIV in Thailand (Brown and Sittitrai, 1994). By the year 2000, researchers estimate that there may be 1.4 million cumulative HIV infections and 480,000 AIDS cases in that country (Cohen, 1994b).

Fig. 5. Cumulative AIDS cases in Thailand, 1979-1994
References: WHO, 1995a

By comparison, South Korea reported only 25 cases of AIDS to the WHO through Dec. 1994 (WHO, 1995a). In serosurveys in that country conducted in 1993, HIV seroprevalence was .008 percent among female prostitutes and .00007 percent among blood donors (Shin et al., 1994).

Evidence From Blood Donor-Recipient Pairs

By the end of 1994, 7,223 cumulative cases of AIDS in the United States resulting from blood transfusions or the receipt of blood components or tissue had been reported to the CDC (CDC, 1995a). Virtually all of these cases can be traced to transfusions before the screening of the blood supply for HIV commenced in 1985 (Jones et al., 1992; Selik et al., 1993).

Compelling evidence supporting a cause-and-effect relationship between HIV and AIDS has come from studies of transfusion recipients with AIDS who have received blood from at least one donor with HIV infection. In the earliest such study (before the discovery of HIV), seven patients with transfusion-acquired AIDS were shown to have received a total of 99 units of blood components. At least one donor to each patient was identified who had AIDS-like symptoms or immunosuppression (Curran et al., 1984).

With the identification of HIV and the development of serologic assays for the virus in 1984, it became possible to trace infected donors (Sarngadharan et al., 1984). The first reports of donor-recipient pairs appeared later that year (Feorino et al., 1984; Groopman et al., 1984). In one instance, HIV was isolated from both donor and recipient, and both had developed AIDS (Feorino et al., 1984); in the other, the recipient was HIV antibody-positive and had developed AIDS, and the donor had culturable virus in his blood and was in a group considered to be at high risk for AIDS (Groopman et al., 1984). Molecular analysis of HIV isolates from these donor-recipient pairs found that the viruses were slightly different but much more similar than would be expected by chance alone (Feorino et al., 1984; Groopman et al., 1984).

In a subsequent study of patients with transfusion-acquired AIDS, 28 of 28 individuals had antibodies to HIV, and each had received blood from an HIV-infected donor (Jaffe et al., 1985b). Similar results were reported from a set of 18 patients with transfusion-acquired AIDS, each of whom had received blood from an HIV-infected donor (McDougal et al., 1985b). Fifteen of the 18 donors in this study had low CD4+/CD8+ T cell ratios, an immune defect seen in pre-AIDS and AIDS patients.

Another group studied seropositive recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of 101 seropositive recipients followed for a median of 55 months after infection, 43 developed AIDS (Ward et al., 1989).

More recently, Australian investigators identified 25 individuals with transfusion-acquired HIV whose infection could be traced to eight individuals who donated blood between 1980 and 1985, and subsequently developed AIDS. By 1992, nine of the 25 HIV-infected blood recipients had developed AIDS, with progression to AIDS and death more rapid among the recipients who received blood from the faster-progressing donors (Ashton et al., 1994).

Impact of HIV Infection on Mortality of Hemophiliacs

As noted above, HIV has been detected in stored blood samples taken from hemophiliac patients in the United States as early as 1978 (Aronson, 1993). By 1984, 55 to 78 percent of U.S. hemophilic patients were HIV-infected (Lederman et al., 1985; Andes et al., 1989). A more recent survey found 46 percent of 9,496 clotting-factor recipients to be HIV-infected, only 9 of whom had a definitive date of seroconversion subsequent to April 1987 (Fricke et al., 1992). By Dec. 31, 1994, 3,863 individuals in the United States with hemophilia or coagulation disorders had been diagnosed with AIDS (CDC, 1995a).

The impact of HIV on the life expectancy of hemophiliacs has been dramatic. In a retrospective study of mortality among 701 hemophilic patients in the United States, median life expectancy for males with hemophilia increased from 40.9 years at the beginning of the century (1900-1920) to a high of 68 years after the introduction of factor therapy (1971 to 1980). In the era of AIDS (1981 to 1990), life expectancy declined to 49 years (Jones and Ratnoff, 1991) (Figure 6).

Fig. 6. The changing prognosis of classic hemophilia. After improvement in survival from 1971-1980 (corresponding to widespread treatment with lyophilized concentrates of Factor VIII), mortality among individuals with Factor VIII deficiency is now increasing, due in large measure to AIDS among people who became HIV-infected during transfusions between 1978 and 1985
Reference: Jones and Ratnoff, 1991.

Another analysis found that the death rate for individuals with hemophilia A in the United States rose three-fold between the periods 1979-1981 and 1987-1989. Median age at death decreased from 57 years in 1979-1981 to 40 years in 1987-1989 (Chorba et al., 1994).

In the United Kingdom, 6,278 males diagnosed with hemophilia were living during the period 1977-91. During 1979-86, 1,227 were infected with HIV during transfusion therapy. Among 2,448 individuals with severe hemophilia, the annual death rate was stable at 8 per 1,000 during 1977-84; during 1985-92 death rates remained at 8 per 1,000 among HIV-seronegative persons with severe hemophilia but rose steeply in those who were seropositive, reaching 81 per 1,000 in 1991-92. Among 3,830 with mild or moderate hemophilia, the pattern was similar, with an initial death rate of 4 per 1,000 in 1977-84, rising to 85 per 1,000 in 1991-92 among seropositive individuals (Darby et al., 1995).

In a British cohort of hemophiliacs infected with HIV between 1979 and 1985 and followed prospectively, 50 of 111 patients had died by the end of 1994, 43 after a diagnosis of AIDS. Only eight of the 61 living patients had CD4+ T cell counts above 500/mm3 (Lee et al., 1995).

Pediatric AIDS

Newborn infants have no behavioral risk factors, yet 6,209 children in the United States have developed AIDS through Dec. 31, 1994 (CDC, 1995a).

Studies have consistently shown that of infants born to HIV-infected mothers, only the 15-40 percent of infants who become HIV-infected before or during birth go on to develop immunosuppression and AIDS, while babies who are not HIV-infected do not develop AIDS (Katz, 1989; d'Arminio et al., 1990; Prober and Gershon, 1991; European Collaborative Study, 1991; Lambert et al., 1990; Lindgren et al. 1991; Andiman et al., 1990; Johnson et al., 1989; Rogers et al., 1989; Hutto et al., 1991). Moreover, in those infants who do acquire HIV and develop AIDS, the rate of disease progression varies directly with the severity of the disease in the mother at the time of delivery (European Collaborative Study, 1992; Blanche et al., 1994).

Almost all infants born to seropositive mothers have detectable HIV antibody, which may persist for as long as 15 months. In most cases, the presence of this antibody does not represent actual infection with HIV, but is antibody from the HIV-infected mother that diffuses across the placenta. In a French study of 22 infants born to HIV-infected mothers, seven babies had antibodies to HIV after one year and all developed AIDS. In these seven infants, the presence of HIV antibodies marked actual infection with HIV, not merely antibodies acquired from the mother. The other 15 children showed a complete loss of maternally acquired HIV antibodies, were not actually infected, and remained healthy. Of the babies who developed AIDS, virus was found in four of four infants tested. HIV was not found in the 15 children who remained healthy (Douard et al., 1989; Gallo, 1991).

In the European Collaborative Study, children born to HIV-seropositive mothers are followed from birth in 10 European centers. A majority of the mothers have a history of injection drug use. A recent report showed that none of the 343 children who had lost maternally transferred HIV antibodies (i.e. they were truly HIV-negative) had developed AIDS or persistent immune deficiency. In contrast, among 64 children who were truly HIV-infected (i.e. they remained HIV antibody positive), 30 percent presented with AIDS within 6 months of age or with oral candidiasis followed rapidly by the onset of AIDS. By their first birthday, 17 percent died of HIV-related diseases (European Collaborative Study, 1991).

In a multicenter study in Bangkok, Thailand, 105 children born to HIV-infected mothers were recently evaluated at 6 months of age (Chearskul et al., 1994). Of 27 infants determined to be HIV-infected by polymerase chain reaction, 24 developed HIV-related symptoms, including six who developed CDC-defined AIDS and four who died with conditions clinically consistent with AIDS. Among 77 exposed but uninfected infants, no deaths occurred.

In a study of 481 infants in Haiti, the survival rate at 18 months was 41 percent for HIV-infected infants, 84 percent among uninfected infants born to seropositive women, and 95 percent among infants born to seronegative women (Boulos et al., 1994).

Investigators have also reported cases of HIV-infected mothers with twins discordant for HIV-infection in which the HIV-infected child developed AIDS, while the other child remained clinically and immunologically normal (Park et al., 1987; Menez-Bautista et al., 1986; Thomas et al., 1990; Young et al., 1990; Barlow and Mok, 1993; Guerrero Vazquez et al., 1993).

Single Source Outbreak of Pediatric AIDS

Other researchers have used molecular epidemiology to find a single source of HIV for an outbreak of pediatric AIDS cases in Russia. In that country between 1988 and 1990, over 250 children were infected with HIV after exposure to non-sterile needles. By June 1994, 43 of these children had died of AIDS (Irova et al., 1993). In a recent report on 22 of these children from two hospitals, 12 had developed AIDS. Molecular analysis of HIV isolates from all 22 children showed the isolates to be very closely related, confirming epidemiological data that these two outbreaks resulted from a single source: an infant born to an HIV-infected mother whose husband was infected in central Africa (Bobkov et al., 1994).

Answering the Skeptics: the "Risk-AIDS" or "Behavioral" Hypothesis

Skeptics of the role of HIV in AIDS have espoused a "risk-AIDS" or a "drug-AIDS" hypothesis (Duesberg, 1987-1994), asserting at different times that factors such as promiscuous homosexual activity; repeated venereal infections and antibiotic treatments; the use of recreational drugs such as nitrite inhalants, cocaine and heroin; immunosuppressive medical procedures; and treatment with the drug AZT are responsible for the epidemic of AIDS.

Such arguments have been repeatedly contradicted. Compelling evidence against the risk-AIDS hypothesis has come from cohort studies of high-risk groups in which all individuals with AIDS-related conditions are HIV-antibody positive, while matched, HIV-antibody negative controls do not develop AIDS or immunosuppression, despite engaging in high-risk behaviors.

In a prospectively studied cohort in Vancouver (Schechter et al., 1993a), 715 homosexual men were followed for a median of 8.6 years. Among 365 HIV-positive individuals, 136 developed AIDS. No AIDS-defining illnesses occurred among 350 HIV-negative men despite the fact that these men reported appreciable levels of nitrite use, other recreational drug use, and frequent receptive anal intercourse. The average rate of CD4+ T cell decline was 50 cells/mm3 per year in the HIV-positive men, while the HIV-negative men showed no decline. Significantly, the decline of CD4+ T cell counts in HIV-positive men and the stability of CD4+ T cell counts in HIV-negative men were apparent whether or not nitrite inhalants were used. There were 101 AIDS-related deaths among the HIV-seropositive men, including six unrelated to HIV infection. In the seronegative group, only two deaths occurred: one heart attack and one suicide. In this study, lifetime prevalences of risk behaviors were similar in the 136 HIV-seropositive men who developed AIDS and in the 226 HIV-seropositive men who did not develop AIDS: use of nitrite inhalants, 88 percent in both groups; use of other illicit drugs, 75 percent and 80 percent, respectively; more than 25 percent of sexual encounters involving receptive anal intercourse, 78 percent and 82 percent, respectively. Among HIV-seronegative men (none of whom developed AIDS), the lifetime prevalences of these behaviors were somewhat lower, but substantial: 56 percent, 74 percent and 58 percent, respectively.

Similar results were reported from the San Francisco Men's Health Study, a cohort of single men recruited in San Francisco in 1984 without regard to sexual preference, lifestyle or serostatus (Ascher et al., 1993a). During 96 months of follow-up, 215 cases of AIDS had occurred among 445 HIV-antibody positive homosexual men, 174 of whom had died. Among 367 antibody-negative homosexual men and 214 antibody-negative heterosexual men, no AIDS cases and eight deaths unrelated to AIDS-defining conditions were observed. The authors found no overall effect of drug consumption, including nitrites, on the development of Kaposi's sarcoma or other AIDS-defining conditions, nor an effect of the extent of the participants' drug use on these conditions. A consistent loss of CD4+ T cells was limited to HIV-positive subjects, among whom there was no discernible difference in CD4+ T cell counts related to drug-taking behavior. Among HIV-seronegative men, moderate or heavy drug users had higher CD4+ T cell counts than non-users.

Observational studies of HIV-infected individuals have found that drug use does not accelerate progression to AIDS (Kaslow et al., 1989; Coates et al., 1990; Lifson et al., 1990; Robertson et al., 1990). In a Dutch cohort of HIV-seropositive homosexual men, no significant differences in sexual behavior or use of cannabis, alcohol, tobacco, nitrite inhalants, LSD or amphetamines were found between men who remained asymptomatic for long periods and those who progressed to AIDS (Keet et al., 1994). Another study, of five cohorts of homosexual men for whom dates of seroconversion were well-documented, found no association between HIV disease progression and history of sexually transmitted diseases, number of sexual partners, use of AZT, alcohol, tobacco or recreational drugs (Veugelers et al., 1994).

Similarly, in the San Francisco City Clinic Cohort, recruited in the late 1970s and early 1980s in conjunction with hepatitis B studies, no consistent differences in exposure to recreational drugs or sexually transmitted diseases were seen between HIV-infected men who progressed to AIDS and those who remained healthy (Buchbinder et al., 1994).

Because many children with AIDS are born to mothers who abuse recreational drugs (Novick and Rubinstein, 1987; European Collaborative Study, 1991), it has been postulated that the mothers' drug consumption is responsible for children developing AIDS (Duesberg, 1987-1994). This theory is contradicted by numerous reports of infants with AIDS born to women infected with HIV through heterosexual contact or transfusions who do not use drugs (CDC, 1995a). As noted above, the only factor that predicts whether a child will develop AIDS is whether he or she is infected with HIV, not maternal drug use.

AIDS and Injection Drug Users

Central to the "risk-AIDS" hypothesis is the notion that chronic injection drug use causes AIDS (Duesberg, 1992), a view that is contradicted by numerous studies.

Although some evidence suggests injection drug use can cause certain immunologic abnormalities, such as reduction in natural killer (NK) cell activity (reviewed in Kreek, 1990), the specific immune deficit that leads to AIDS--a progressive reduction of CD4+ T cells resulting in persistent CD4+ T lymphocytopenia--is rare in HIV-seronegative injection drug users in the absence of other immunosuppressive conditions (Des Jarlais et al., 1993; Weiss et al., 1992).

In a survey of 229 HIV-seronegative injection drug users in New York City, mean CD4+ T cell counts of the group were consistently over 1000/mm3 (Des Jarlais et al., 1993). Only two individuals had two CD4+ T cell measurements of fewer than 300/mm3, one of whom died with cardiac disease and non-Hodgkin's lymphoma listed as the cause of death. In a study of 180 HIV-seronegative injection drug users in New Jersey, the participants' average CD4+ T cell count was 1169/mm3 (Weiss et al., 1992). Two of these individuals, both with generalized lymphocytopenia, had CD4+ T cell counts less than 300/mm3.

In the MACS, median CD4+ T cell counts of 63 HIV-seronegative injection drug users rose from 1061/mm3 to 1124/mm3 in a 15 to 21 month follow-up period (Margolick et al., 1992). In a cross-sectional study, 11 HIV-seronegative, long-term heroin addicts had mean CD4+ T cell counts of 1500/mm3, while 11 healthy controls had CD4+ T cell counts of 820 cells/mm3 (Novick et al., 1989).

Recent data also refute the notion that a certain lifetime dosage of injection drugs is sufficient to cause AIDS in HIV-seronegative individuals. In a Dutch study, investigators compared 86 HIV-seronegative individuals who had been injecting drugs for a mean of 7.6 years with 70 HIV-seropositive people who had injected drugs for a mean of 9.1 years. Upon enrollment in 1989, CD4+ T cell counts were 914/mm3 in the HIV-seronegative group, and 395/mm3 in the seropositive group. By 1994, there were 25 deaths attributable to AIDS-defining conditions in the seropositive group; among HIV-seronegative individuals, eight deaths occurred, none due to AIDS-defining diseases (Cohen, 1994a).

Excess mortality among HIV-infected injection drug users as compared to HIV-seronegative users has also been observed by other investigators. In a prospective Italian study of 2,431 injection drug users enrolled in drug treatment programs from 1985 to 1991, HIV-seropositive individuals were 4.5 times more likely to die than HIV-seronegative subjects (Zaccarelli et al., 1994). No deaths due to AIDS-defining conditions were seen among 1,661 HIV-seronegative individuals, 41 of whom died of other conditions, predominantly overdose, liver disease and accidents. Among 770 individuals who were HIV-seropositive at study entry or who seroconverted during the study period, 89 died of AIDS-related conditions and 52 of other conditions.

In HIV-seropositive individuals, a number of investigators have found no statistical association between injection drug use and decline of CD4+ T cell counts (Galli et al., 1989, 1991; Schoenbaum et al., 1989; Margolick et al., 1992, 1994; Montella et al., 1992; Alcabes et al., 1993b, 1994; Galai et al., 1995), nor a difference in disease progression between active versus former users of injection drugs (Weber et al., 1990; Galli et al., 1991; Montella et al., 1992; Italian Seroconversion Study, 1992).

Taken together, these studies suggest that any negative effects of injection drugs on CD4+ T cell levels are limited and may explain why many investigators have found that HIV-seropositive injection drug users have rates of disease progression that are similar to other HIV-infected individuals (Rezza et al., 1990; Montella et al., 1992; Galli et al., 1989; Selwyn et al., 1992; Munoz et al., 1992; Italian Seroconversion Study, 1992; MAP Workshop, 1993; Pezzotti et al., 1992; Margolick et al., 1992, 1994; Alcabes, 1993b, 1994; Galai et al., 1995).

Sex and the AIDS Epidemic

It has been asserted ". . . in America, only promiscuity aided by aphrodisiac and psychoactive drugs, practiced mostly by 20 to 40 year-old male homosexuals and some heterosexuals, seems to correlate with AIDS diseases" (Duesberg, 1991). Even a cursory review of history provides evidence to the contrary: such behaviors have existed for decades --in some cases centuries--and have increased only in a relative sense in recent years, if at all, whereas AIDS clearly is a new phenomenon.

If promiscuity were a cause of AIDS, one would have expected cases to have occurred among prostitutes (male or female) prior to 1978. Reports of such cases are lacking, even though prostitution has been present in most if not all cultures throughout history.

In this country, trends in gonorrheal infections suggest that extramarital sexual activity was extensive in the pre-AIDS era. Cases of gonorrhea in the United States peaked at approximately 1 million in 1978; between 250,000 and 530,000 cases were reported each year in the 1960s, approximately 250,000 cases each year in the 1950s, and between 175,000 and 380,000 cases annually in the 1940s (CDC, 1987c, 1993b). Despite the frequency of sexually transmitted diseases, only a handful of documented cases of AIDS in the United States prior to 1978 have been reported.

Historians, archaeologists and sociologists have documented extensive homosexual activity dating from the ancient Greeks to the well-established homosexual subculture in the United States in the 20th century (Weinberg and Williams, 1974; Gilbert, 1980-81; Saghir and Robins, 1973; Reinisch et al., 1990; Doll et al., 1990; Katz, 1992; Friedman and Downey, 1994). Depictions of anal intercourse, both male and female, can be found in the art and literature of numerous cultures on all inhabited continents (Reinisch et al., 1990). In the 1940s, Kinsey et al. reported that 37 percent of all American males surveyed had at least some overt homosexual experience to the point of orgasm between adolescence and old age and that 10 percent of men were exclusively or predominantly homosexual between the ages of 16 and 55 (Kinsey et al., 1948). More recent surveys have found that 2 to 5 percent of men are homosexual or bisexual (reviewed in Friedman and Downey, 1994; Seidman and Rieder, 1994; Laumann, 1994).

Many homosexuals had multiple sexual partners in the pre-AIDS era: a 1969 survey found that more than 40 percent of white homosexual males and one-third of black homosexual males had at least 500 partners in their lifetime, and an additional one-fourth reported between 100 and 500 partners (Bell and Weinberg, 1978). A majority of these men reported that more than half their partners had been strangers before the sexual encounters (Bell and Weinberg, 1978). Further evidence of extensive homosexual behavior in the years preceding the AIDS epidemic comes from reports of numerous cases of rectal gonorrheal and anal herpes simplex virus infections among men (Jefferiss, 1956; Scott and Stone, 1966; Pariser and Marino, 1970; Owen and Hill, 1972; British Cooperative Clinical Group, 1973; Jacobs, 1976; Judson et al., 1977; Merino and Richards, 1977; McMillan and Young, 1978).

Drug Use in the Pre-AIDS Era

A temporal association between the onset of extensive use of recreational drugs and the AIDS epidemic is also lacking. The widespread use of opiates in the United States has existed since the middle of the 19th century (Courtwright, 1982); as many as 313,000 Americans were addicted to opium and morphine prior to 1914. Heroin use spread throughout the country in the 1920s and 1930s (Courtwright, 1982), and the total number of active heroin users peaked at about 626,000 in 1971 (Greene et al., 1975; Friedland, 1989). Opiates were initially administered by oral or inhalation routes, but by the 1920s addicts began to inject heroin directly into their veins (Courtwright, 1982). In 1940, intravenous use of opiates was seen in 80 percent of men admitted to a large addiction research center in Kentucky (Friedland, 1989).

While cocaine use increased markedly during the 1970s (Kozel and Adams, 1986), the use of the drug, frequently with morphine, is well-documented in the United States since the late 19th century (Dale, 1903; Ashley, 1975; Spotts and Shontz, 1980). For example, a survey in 1902 reported that only 3 to 8 percent of the cocaine sold in New York, Boston and other cities went into the practice of medicine or dentistry (Spotts and Shontz). After a period of relative obscurity, cocaine became increasingly popular in the late 1950s and 1960s. Over 70 percent of 1,100 addicts at the addiction research center in Kentucky in 1968 and 1969 reported use or abuse of cocaine (Chambers, 1974).

The recreational use of nitrite inhalants ("poppers") also predates the AIDS epidemic. Reports of the widespread use of these drugs by young men in the 1960s were the impetus for the reinstatement by the Food and Drug Administration of the prescription requirement for amyl nitrite in 1968 (Israelstam et al., 1978; Haverkos and Dougherty, 1988). Since the early years of the AIDS epidemic, the use of nitrite inhalants has declined dramatically among homosexual men, yet the number of AIDS cases continues to increase (Ostrow et al., 1990, 1993; Lau et al., 1992).

In the general population, the number of individuals aged 25 to 44 years reporting current use of marijuana, cocaine, inhalants, hallucinogens and cigarettes declined between 1974 and 1992, while the AIDS epidemic worsened (Substance Abuse and Mental Health Services Administration, 1994).

AZT and AIDS

Although some individuals maintain that treatment with zidovudine (AZT) has compounded the AIDS epidemic (Duesberg, 1992), published reports of both placebo-controlled clinical trials and observational studies provide data to the contrary (Table 4).

Table 4. Major placebo-controlled trials of zidovudine (AZT) monotherapy in HIV-infectedpatients without AIDS

Early symptomatic HIV infection

Study	Reference	CD4+ T cell count at study entry (cells/mm3)	Daily dose zidovudine (milligrams)	Avg. Duration of follow-up (months)	Number in analysis ZDV/imm/ P/def	No. progressingto AIDS or death ZDV/imm/P/def
ACTG 016	Fischl, 1990	200-800	1200	11	360/351	7/21
VA 298	Hamilton, 1992	200-500	1500	28	170/168	38/48

Asymptomatic HIV infection

Study	Reference	CD4+ T cell count at study entry (cells/mm3)	Daily dose zidovudine (milligrams)	Avg. Duration of follow-up (months)	Number in analysis ZDV/imm/ P/def	No. progressingto AIDS or death ZDV/imm/P/def
ACTG 019‡	Volberding, 1990	< 500	1500 500	13	457,453/428	14,11/33
-	Volberding, 1994¶ (extended follow-up)	< 500	1500 500	31	530,542/493	75,79/78
EACG 020	Cooper, 1993	< 400	1000	21	495/489	6/9
ACTG 036	Merigan, 1991	< = 500	1500	10	92/101	3/6
EA hemophilia	Mannucci, 1994	100-400†	1000	21	69/71	5/4
EACG 017	Mulder, 1994	200-400†	1000	14	167/162	11/12
Concorde	Concorde, 1994	any	1000	36	877/872	176/171

The Concorde trial and VA 298 compared immediate (imm) and deferred (def) use of zidovudine (ZDV); the other trials compared zidovudine (ZDV) and placebo (P).
† Or p24 antigenemia.
‡ In ACTG 019, original treatment group included placebo, 500 mg. ZDV/day or 1500 mg. ZDV/day.
¶ After the unblinding of the original randomized trial in 1989, subjects in each original arm were offered a daily dose of 500 mg. open-label zidovudine.
Modified from Concorde Coordinating Committee, 1994.

In patients with symptomatic HIV disease, for whom a beneficial effect is measured in months, AZT appears to slow disease progression and prolong life, according to double-blind, placebo-controlled clinical studies (reviewed in Sande et al., 1993; McLeod and Hammer, 1992; Volberding and Graham, 1994). A clinical trial known as BW 002 compared AZT with placebo in 282 patients with AIDS or advanced signs or symptoms of HIV disease. In this study, which led to the approval of AZT by the FDA, only one of 145 patients treated with AZT died compared with 19 of 137 placebo recipients in a six month period. Opportunistic infections occurred in 24 AZT recipients and 45 placebo recipients. In addition to reducing mortality, AZT was shown to have reduced the frequency and severity of AIDS-associated opportunistic infections, improved body weight, prevented deterioration in Karnofsky performance score, and increased counts of CD4+ T lymphocytes in the peripheral blood (Fischl et al., 1987; Richman et al., 1987). Continued follow-up in 229 of these patients showed that the survival benefit of AZT extended to at least 21 months after the initiation of therapy; survival in the original treatment group was 57.6 percent at that time, whereas survival among members of the original placebo group was 51.5 percent at nine months (Richman and Andrews, 1988; Fischl et al., 1989).

In another placebo-controlled study known as ACTG 016, which enrolled 711 symptomatic HIV-infected patients with CD4+ T cell counts between 200 and 500 cells/mm3, those taking AZT were less likely to experience disease progression than those on placebo during a median study period of 11 months (Fischl et al., 1990). In this study, no difference in disease progression was noted among participants who began the trial with CD4+ T cell counts greater than 500/mm3.

A Veteran's Administration study of 338 individuals with early symptoms of HIV disease and CD4+ T cell counts between 200 and 500 cells/mm3 found that immediate therapy significantly delayed disease progression compared with deferred therapy, but did not lengthen (or shorten) survival after an average study period of more than two years (Hamilton et al., 1992).

Among asymptomatic HIV-infected individuals, several placebo-controlled clinical trials suggest that AZT can delay disease progression for 12 to 24 months but ultimately does not increase survival. Significantly, long-term follow-up of persons participating in these trials, although not showing prolonged benefit of AZT, has never indicated that the drug increases disease progression or mortality (reviewed in McLeod and Hammer, 1992; Sande et al., 1993; Volberding and Graham, 1994). The lack of excess AIDS cases and death in the AZT arms of these large trials effectively rebuts the argument that AZT causes AIDS.

During a 4.5 year follow-up period (mean 2.6 years) of a trial known as ACTG 019, no differences were seen in overall survival between AZT and placebo groups among 1,565 asymptomatic patients entering the study with fewer than 500 CD4+ T cells/mm3 (Volberding et al., 1994). In that study, AZT was superior to placebo in delaying progression to AIDS or advanced ARC for approximately one year, and a more prolonged benefit was seen among a subset of patients.

The Concorde study in Europe enrolled 1,749 asymptomatic patients with CD4+ T cell counts less than 500/mm3. In that study, no statistically significant differences in progression to advanced disease were observed after three years between individuals taking AZT immediately and those who deferred AZT therapy or did not take the drug (Concorde Coordinating Committee, 1994). However, the rate of progression to death, AIDS or severe ARC was slower among the "immediate" AZT group during the first year of therapy. Although the Concorde study did not show a significant benefit over time with the early use of AZT, it clearly demonstrated that AZT was not harmful to the patients in the "immediate" AZT group as compared to the "deferred" AZT group.

A European-Australian study (EACG 020) of 993 patients with CD4+ T cell counts greater than 400/mm3 showed no differences between AZT and placebo arms of the trial during a median study period of 94 weeks, although AZT did delay progression to certain clinical and immunological endpoints for up to three years (Cooper et al., 1993). Both this study and the Concorde study reported little severe AZT-related hematologic toxicity at doses of 1,000 mg/day, which is twice the recommended daily dose in the United States.

Uncontrolled studies have found increased survival and/or reduced frequency of opportunistic infections in patients with HIV disease and AIDS who were treated with AZT or other anti-retrovirals (Creagh-Kirk et al., 1988; Moore et al., 1991a,b; Ragni et al., 1992; Schinaia et al., 1991; Koblin et al., 1992; Graham et al., 1991, 1992, 1993; Longini, 1993; Vella et al., 1992, 1994; Saah et al., 1994; Bacellar et al., 1994). In the Multicenter AIDS Cohort Study, for example, HIV-infected individuals treated with AZT had significantly reduced mortality and progression to AIDS for follow-up intervals of six, 12, 18 and 24 months compared to those not taking AZT, even after adjusting for health status, CD4+ T cell counts and PCP prophylaxis (Graham et al., 1991, 1992).

In addition, several cohort studies show that life expectancy of individuals with AIDS has increased since the use of AZT became common in 1986-87. Among 362 homosexual men in hepatitis B vaccine trial cohorts in New York City, San Francisco and Amsterdam, the time from seroconversion to death, a period not influenced by variations in diagnosing AIDS, has lengthened slightly in recent years (Hessol et al., 1994). In a Dutch study of 975 males and females with HIV infection, median survival with AIDS increased from nine months in 1982-1985, to 26 months in 1990 (Bindels et al., 1994). Even taking into consideration the benefits of improved PCP prophylaxis and treatment, if AZT were contributing to or causing disease, one would expect a decrease in survival figures, rather than an increase that parallels the use of AZT.

In an analysis from the San Francisco Men's Health Study, the investigators note that 169 (73 percent) of 233 AIDS patients had been treated with AZT at one time or another. However, 90 (53 percent of the 169) were diagnosed with clinical AIDS before beginning AZT treatment, and another 51 (30 percent of the 169) had CD4+ T cell counts lower than 200/mm3 before initiation of AZT treatment (Ascher et al., 1995). The authors conclude, "These data are not consistent with the hypothesis of a causal role for AZT in AIDS."

Disease Progression Despite Antibodies

It has been argued that HIV cannot cause AIDS because the body develops HIV-specific antibodies following primary infection (Duesberg, 1992). This reasoning ignores numerous examples of viruses other than HIV that can be pathogenic after evidence of immunity appears (Oldstone, 1989). Primary poliovirus infection is a classic example of a disease in which high titers of neutralizing antibodies develop in all infected individuals, yet a small percentage of individuals develop subsequent paralysis (Kurth, 1990). Measles virus may persist for years in brain cells, eventually causing a chronic neurological disease despite the presence of antibodies (Gershon, 1990). Viruses such as cytomegalovirus, herpes simplex and varicella zoster may be activated after years of latency even in the presence of abundant antibodies (Weiss and Jaffe, 1990). Lentiviruses with long and variable latency periods, such as visna virus in sheep, cause central nervous system damage even after the specific production of neutralizing antibodies (Haase, 1990). Furthermore, it is now well-documented that HIV can mutate rapidly to circumvent immunologic control of its replication.

Risks Associated With Transfusion

It has been argued that AIDS among transfusion recipients is due to underlying diseases that necessitated the transfusion, rather than to HIV (Duesberg, 1991). This theory is contradicted by a report by the Transfusion Safety Study Group, which compared HIV-negative and HIV-positive blood recipients who had been given transfusions for similar diseases. Approximately three years after the transfusion, the mean CD4+ T cell count in 64 HIV-negative recipients was 850/mm3, while 111 HIV-seropositive individuals had average CD4+ T cell counts of 375/mm3 (Donegan et al., 1990). By 1993, there were 37 cases of AIDS in the HIV-infected group, but not a single AIDS-defining illness in the HIV-seronegative transfusion recipients (Cohen, 1994d).

People have received blood transfusions for decades; however, as discussed above, AIDS-like symptoms were extraordinarily rare before the appearance of HIV. Recent surveys have shown that AIDS-like symptoms remain very rare among transfusion recipients who are HIV-seronegative and their sexual contacts. In one study of transfusion safety, no AIDS-defining illnesses were seen among 807 HIV-negative recipients of blood or blood products, or 947 long-term sexual or household contacts of these individuals (Aledort et al., 1993).

In addition, through 1994, the CDC had received reports of 628 cases of AIDS in individuals whose primary risk factor was sex with an HIV-infected transfusion recipient (CDC, 1995a), a finding not explainable by the "risk-AIDS" hypothesis.

Exposure to Factor VIII

It has also been argued that cumulative exposure to foreign proteins in Factor VIII concentrates leads to CD4+ T cell depletion and AIDS in hemophiliacs (Duesberg, 1992). This view is contradicted by several large studies. Among HIV-seronegative patients with hemophilia A enrolled in the Transfusion Safety Study, no significant differences in CD4+ T cell counts were noted between 79 patients with no or minimal factor treatment and 53 patients with the largest amount of lifetime treatments (cumulative totals in the latter group ranged from 100,000 to 2,000,000 U in two years) (Hassett et al., 1993). Although the CD4+ T cell counts seen in the low- and high- groups (756/mm3 and 718/mm3, respectively) were 20 to 25 percent lower than controls, such levels are still within the normal range.

In a report from the Multicenter Hemophilia Cohort Study, the mean CD4+ T cell counts among 161 HIV-seronegative hemophiliacs was 784/mm3; among 715 HIV-seropositive hemophiliacs, the mean CD4+ T cell count was 253/mm3 (Lederman et al., 1995).

In another study, no instances of AIDS-defining illnesses were seen among 402 HIV-seronegative hemophiliacs treated with factor therapy or in 83 hemophiliacs who received no treatment subsequent to 1979 (Aledort et al., 1993; Mosely et al., 1993).

In a retrospective study of patients with severe hemophilia A, the rate of CD4+ T cell loss was 31.4 every six months for 41 HIV-seropositive individuals without AIDS and 49.7 every six months for 14 HIV-seropositive individuals with AIDS. In contrast, among 28 HIV-seronegative individuals, CD4+ T cell counts increased at a rate of 13.1 cells/six months (Becherer et al., 1990).

In a study of children and adolescents with hemophilia, the median CD4+ T cell count of 126 HIV-seronegative individuals was 895/mm3 at study entry; no individuals had CD4+ T cell counts below 200/mm3. In contrast, 26 percent of seropositive children had CD4+ T cell counts of less than 200/mm3; the mean CD4+ T cell count for seropositive children was 423/mm3 (Jason et al., 1994).

Although some reports have suggested that high-purity Factor VIII concentrates are associated with a slower rate of CD4+ T cell decline in HIV-infected hemophiliacs than products of low and intermediate purity (Hilgartner et al., 1993; Goldsmith et al., 1991; de Biasi et al., 1991), other studies have shown no such benefit (Mannucci et al., 1992; Gjerset et al., 1994). In a study of 525 HIV-infected hemophiliacs, Transfusion Safety Study investigators found that neither the purity nor the amount of Factor VIII therapy had a deleterious effect on CD4+ T cell counts (Gjerset et al., 1994). Similarly, the Multicenter Hemophilia Cohort Study found no association between the cumulative dose of plasma concentrate and incidence of AIDS among 242 HIV-infected hemophiliacs and thus "no support for cofactor hypotheses involving either antigen stimulation or inoculum size" (Goedert et al., 1989).

In addition to the evidence from the cohort studies cited above, it should be noted that 10 to 20 percent of wives and sex partners of male HIV-positive hemophiliacs in the United States are also HIV-infected (Pitchenik et al., 1984; Kreiss et al., 1985; Peterman et al., 1988; Smiley et al., 1988; Dietrich and Boone, 1990; Lusher et al., 1991). Through December 1994, the CDC had received reports of 266 cases of AIDS in those who had sex with a person with hemophilia (CDC, 1995a). These data cannot be explained by a non-infectious theory of AIDS etiology.

Distribution of AIDS Cases

Certain skeptics maintain that the distribution of AIDS cases casts doubt on HIV as the cause of the syndrome. They claim infectious microbes are not gender-specific, yet relatively few people with AIDS are women (Duesberg, 1992).

In fact, the distribution of AIDS cases, whether in the United States or elsewhere in the world, invariably mirrors the prevalence of HIV in a population (U.S. Bureau of the Census, 1994). In the United States, HIV first appeared in populations of homosexual men and injection drug users, a majority of whom are male (Curran et al., 1988). Because HIV is spread primarily through sex or by the exchange of HIV-contaminated needles during injection drug use, it is not surprising that a majority of U.S. AIDS cases have occurred in men.

Increasingly, however, women are becoming HIV-infected, usually through the exchange of HIV-contaminated needles or sex with an HIV-infected male (Vermund, 1993b; CDC, 1995a). As the number of HIV-infected women has risen, so too have the number of female AIDS cases. In the United States, the proportion of AIDS cases among women has increased from 7 percent in 1985 to 18 percent in 1994. AIDS is now the fourth leading cause of death among women aged 25 to 44 in the United States (CDC, 1994).

In Africa, HIV was first recognized in sexually active heterosexuals, and in some parts of Africa AIDS cases have occurred as frequently in women as in men (Quinn et al., 1986; Mann, 1992a). In Zambia, for example, the 29,734 AIDS cases reported to the WHO through October 20, 1993, were equally divided among males and females (WHO, 1995a,b).

AIDS in Africa

One vocal skeptic of the role of HIV in AIDS argues that, in Africa, AIDS is nothing more than a new name for old diseases (Duesberg, 1991). It is true that the diseases that have come to be associated with AIDS in Africa--wasting, diarrheal diseases and TB--have long been severe burdens there. However, high rates of mortality from these diseases, formerly confined to the elderly and malnourished, are now common among HIV-infected young and middle-aged people (Essex, 1994). In a recent study of more than 9,000 individuals in rural Uganda, people testing positive for HIV antibodies were 60 times as likely to die during the subsequent two-year observation period as were otherwise similar persons who tested negative (Mulder et al., 1994b). Large differences in mortality were also seen between HIV-seropositive and HIV-seronegative individuals in another large Ugandan cohort (Sewankambo et al., 1994).

Elsewhere in Africa findings are similar. One study of 1,400 Rwandan women tested for HIV during pregnancy found that HIV infected women were 20 times more likely to die in the two years following pregnancy than their HIV-negative counterparts (Lindan et al., 1992). In another study in Rwanda, 215 HIV-seropositive women and 216 HIV-seronegative women were followed prospectively for up to four years, during which time 21 women developed AIDS (WHO definition), all of them in the HIV-seropositive group. The mortality rate among the HIV-seropositive women was nine times higher than seen among the HIV-seronegative women (Leroy et al., 1995)

In Zaire, investigators found that families in which the mother was HIV-1 seropositive experienced a five- to 10-fold higher maternal, paternal and early childhood mortality rate than families in which the mother was HIV-seronegative (Ryder et al., 1994b). In another study in Zaire, infants with HIV infection were shown to have an 11-fold increased risk of death from diarrhea compared with uninfected children (Thea et al., 1993). In patients with pulmonary tuberculosis in Cote d'Ivoire, HIV-seropositive individuals were 17 times more likely to die than HIV-seronegative individuals (Ackah et al., 1995).

The extraordinary death rates among HIV-infected individuals confirm that the virus is an important cause of premature mortality in Africa (Dondero and Curran, 1994).

Conclusion

HIV and AIDS have been repeatedly linked in time, place and population group; the appearance of HIV in the blood supply has preceded or coincided with the occurrence of AIDS cases in every country and region where AIDS has been noted. Among individuals without HIV, AIDS-like symptoms are extraordinarily rare, even in populations with many AIDS cases. Individuals as different as homosexual men, elderly transfusion recipients, heterosexual women, drug-using heterosexual men and infants have all developed AIDS with only one common denominator: infection with HIV. Laboratory workers accidentally exposed to highly concentrated HIV and health care workers exposed to HIV-infected blood have developed immunosuppression and AIDS with no other risk factor for immune dysfunction. Scientists have now used PCR to find HIV in virtually every patient with AIDS and to show that HIV is present in large and increasing amounts even in the pre-AIDS stages of HIV disease. Researchers also have demonstrated a correlation between the amount of HIV in the body and progression of the aberrant immunologic processes seen in people with AIDS.

Despite this plethora of evidence, the notion that HIV does not cause AIDS continues to find a wide audience in the popular press, with potential negative impact on HIV-infected individuals and on public health efforts to control the epidemic. HIV-infected individuals may be convinced to forego anti-HIV treatments that can forestall the onset of the serious infections and malignancies of AIDS (Edelman et al., 1991). Pregnant HIV-infected women may dismiss the option of taking AZT, which can reduce the likelihood of transmission of HIV from mother to infant (Connor et al., 1994; Boyer et al., 1994).

People may be dissuaded from being tested for HIV, thereby missing the opportunity, early in the course of disease, for counselling as well as for treatment with drugs to prevent AIDS-related infections such as PCP. Such prophylactic measures prolong survival and improve the quality of life of HIV-infected individuals (CDC, 1992b).

Most troubling is the prospect that individuals will discount the threat of HIV and continue to engage in risky sexual behavior and needle sharing. If public health messages on AIDS prevention are diluted by the misconception that HIV is not responsible for AIDS, otherwise preventable cases of HIV infection and AIDS may occur, adding to the global tragedy of the epidemic.

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The Evidence that HIV Causes AIDS: An NIAID Fact Sheet

Nathan Geffen — Sat, 25 Apr 2009 11:04:08 +0000

The Evidence That HIV Causes AIDS

BACKGROUND

The acquired immunodeficiency syndrome (AIDS) was first recognized in 1981 and has since become a major worldwide pandemic. AIDS is caused by the human immunodeficiency virus (HIV). By leading to the destruction and/or functional impairment of cells of the immune system, notably CD4+ T cells, HIV progressively destroys the body's ability to fight infections and certain cancers.

An HIV-infected person is diagnosed with AIDS when his or her immune system is seriously compromised and manifestations of HIV infection are severe. The U.S. Centers for Disease Control and Prevention (CDC) currently defines AIDS in an adult or adolescent age 13 years or older as the presence of one of 26 conditions indicative of severe immunosuppression associated with HIV infection, such as Pneumocystis carinii pneumonia (PCP), a condition extraordinarily rare in people without HIV infection. Most other AIDS-defining conditions are also "opportunistic infections" which rarely cause harm in healthy individuals. A diagnosis of AIDS also is given to HIV-infected individuals when their CD4+ T-cell count falls below 200 cells/cubic millimeter (mm³) of blood. Healthy adults usually have CD4+ T-cell counts of 600-1,500/mm³ of blood. In HIV-infected children younger than 13 years, the CDC definition of AIDS is similar to that in adolescents and adults, except for the addition of certain infections commonly seen in pediatric patients with HIV. (CDC. MMWR 1992;41(RR-17):1; CDC. MMWR 1994;43(RR-12):1).

In many developing countries, where diagnostic facilities may be minimal, healthcare workers use a World Health Organization (WHO) AIDS case definiton based on the presence of clinical signs associated with immune deficiency and the exclusion of other known causes of immunosuppression, such as cancer or malnutrition. An expanded WHO AIDS case definition, with a broader spectrum of clinical manifestations of HIV infection, is employed in settings where HIV antibody tests are available (WHO. Wkly Epidemiol Rec. 1994;69:273).

As of the end of 2000, an estimated 36.1 million people worldwide - 34.7 million adults and 1.4 million children younger than 15 years - were living with HIV/AIDS. Through 2000, cumulative HIV/AIDS-associated deaths worldwide numbered approximately 21.8 million - 17.5 million adults and 4.3 million children younger than 15 years. In the United States, an estimated 800,000 to 900,000 people are living with HIV infection. As of December 31, 1999, 733,374 cases of AIDS and 430,441 AIDS-related deaths had been reported to the CDC. AIDS is the fifth leading cause of death among all adults aged 25 to 44 in the United States. Among African-Americans in the 25 to 44 age group, AIDS is the leading cause of death for men and the second leading cause of death for women (UNAIDS. AIDS epidemic update: December 2000; CDC. HIV/AIDS Surveillance Report 1999;11[2]:1; CDC. MMWR 1999;48[RR13]:1).

This document summarizes the abundant evidence that HIV causes AIDS. Questions and answers at the end of this document address the specific claims of those who assert that HIV is not the cause of AIDS.

EVIDENCE THAT HIV CAUSES AIDS

HIV fulfills Koch's postulates as the cause of AIDS.

Among many criteria used over the years to prove the link between putative pathogenic (disease-causing) agents and disease, perhaps the most-cited are Koch's postulates, developed in the late 19th century. Koch's postulates have been variously interpreted by many scientists, and modifications have been suggested to accommodate new technologies, particularly with regard to viruses (Harden. Pubbl Stn Zool Napoli [II] 1992;14:249; O'Brien, Goedert. Curr Opin Immunol 1996;8:613). However, the basic tenets remain the same, and for more than a century Koch's postulates, as listed below, have served as the litmus test for determining the cause of any epidemic disease:

Epidemiological association: the suspected cause must be strongly associated with the disease.
Isolation: the suspected pathogen can be isolated - and propagated - outside the host.
Transmission pathogenesis: transfer of the suspected pathogen to an uninfected host, man or animal, produces the disease in that host.

With regard to postulate #1, numerous studies from around the world show that virtually all AIDS patients are HIV-seropositive; that is they carry antibodies that indicate HIV infection. With regard to postulate #2, modern culture techniques have allowed the isolation of HIV in virtually all AIDS patients, as well as in almost all HIV-seropositive individuals with both early- and late-stage disease. In addition, the polymerase chain (PCR) and other sophisticated molecular techniques have enabled researchers to document the presence of HIV genes in virtually all patients with AIDS, as well as in individuals in earlier stages of HIV disease.

Postulate #3 has been fulfilled in tragic incidents involving three laboratory workers with no other risk factors who have developed AIDS or severe immunosuppression after accidental exposure to concentrated, cloned HIV in the laboratory. In all three cases, HIV was isolated from the infected individual, sequenced and shown to be the infecting strain of virus. In another tragic incident, transmission of HIV from a Florida dentist to six patients has been documented by genetic analyses of virus isolated from both the dentist and the patients. The dentist and three of the patients developed AIDS and died, and at least one of the other patients has developed AIDS. Five of the patients had no HIV risk factors other than multiple visits to the dentist for invasive procedures (O'Brien, Goedert. Curr Opin Immunol 1996;8:613; O'Brien, 1997; Ciesielski et al. Ann Intern Med 1994;121:886).

In addition, through December 1999, the CDC had received reports of 56 health care workers in the United States with documented, occupationally acquired HIV infection, of whom 25 have developed AIDS in the absence of other risk factors. The development of AIDS following known HIV seroconversion also has been repeatedly observed in pediatric and adult blood transfusion cases, in mother-to-child transmission, and in studies of hemophilia, injection-drug use and sexual transmission in which seroconversion can be documented using serial blood samples (CDC. HIV AIDS Surveillance Report 1999;11[2]:1; AIDS Knowledge Base, 1999). For example, in a 10-year study in the Netherlands, researchers followed 11 children who had become infected with HIV as neonates by small aliquots of plasma from a single HIV-infected donor. During the 10-year period, eight of the children died of AIDS. Of the remaining three children, all showed a progressive decline in cellular immunity, and two of the three had symptoms probably related to HIV infection (van den Berg et al. Acta Paediatr 1994;83:17).

Koch's postulates also have been fulfilled in animal models of human AIDS. Chimpanzees experimentally infected with HIV have developed severe immunosuppression and AIDS. In severe combined immunodeficiency (SCID) mice given a human immune system, HIV produces similar patterns of cell killing and pathogenesis as seen in people. HIV-2, a less virulent variant of HIV which causes AIDS in people, also causes an AIDS-like syndrome in baboons. More than a dozen strains of simian immunodeficiency virus (SIV), a close cousin of HIV, cause AIDS in Asian macaques. In addition, chimeric viruses known as SHIVs, which contain an SIV backbone with various HIV genes in place of the corresponding SIV genes, cause AIDS in macaques. Further strengthening the association of these viruses with AIDS, researchers have shown that SIV/SHIVs isolated from animals with AIDS cause AIDS when transmitted to uninfected animals (O'Neil et al. J Infect Dis 2000;182:1051; Aldrovandi et al. Nature 1993;363:732; Liska et al. AIDS Res Hum Retroviruses 1999;15:445; Locher et al. Arch Pathol Lab Med 1998;22:523; Hirsch et al. Virus Res 1994;32:183; Joag et al. J Virol 1996;70:3189).

AIDS and HIV infection are invariably linked in time, place and population group.

Historically, the occurence of AIDS in human populations around the world has closely followed the appearance of HIV. In the United States, the first cases of AIDS were reported in 1981 among homosexual men in New York and California, and retrospective examination of frozen blood samples from a U.S. cohort of gay men showed the presence of HIV antibodies as early as 1978, but not before then. Subsequently, in every region, country and city where AIDS has appeared, evidence of HIV infection has preceded AIDS by just a few years (CDC. MMWR 1981;30:250; CDC. MMWR 1981;30:305; Jaffe et al. Ann Intern Med 1985;103:210; U.S. Census Bureau; UNAIDS).

Many studies agree that only a single factor, HIV, predicts whether a person will develop AIDS.

Other viral infections, bacterial infections, sexual behavior patterns and drug abuse patterns do not predict who develops AIDS. Individuals from diverse backgrounds, including heterosexual men and women, homosexual men and women, hemophiliacs, sexual partners of hemophiliacs and transfusion recipients, injection-drug users and infants have all developed AIDS, with the only common denominator being their infection with HIV (NIAID, 1995).

In cohort studies, severe immunosuppression and AIDS-defining illnesses occur almost exclusively in individuals who are HIV-infected.

For example, analysis of data from more than 8,000 participants in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) demonstrated that participants who were HIV-seropositive were 1,100 times more likely to develop an AIDS-associated illness than those who were HIV-seronegative. These overwhelming odds provide a clarity of association that is unusual in medical research (MACS and WIHS Principal Investigators, 2000).

In a Canadian cohort, investigators followed 715 homosexual men for a median of 8.6 years. Every case of AIDS in this cohort occurred in individuals who were HIV-seropositive. No AIDS-defining illnesses occurred in men who remained negative for HIV antibodies, despite the fact that these individuals had appreciable patterns of illicit drug use and receptive anal intercourse (Schechter et al. Lancet 1993;341:658).

Before the appearance of HIV, AIDS-related diseases such as PCP, KS and MAC were rare in developed countries; today, they are common in HIV-infected individuals.

Prior to the appearance of HIV, AIDS-related conditions such as Pneumocystis carinii pneumonia (PCP), Kaposi's sarcoma (KS) and disseminated infection with the Mycobacterium avium complex (MAC) were extraordinarily rare in the United States. In a 1967 survey, only 107 cases of PCP in the United States had been described in the medical literature, virtually all among individuals with underlying immunosuppressive conditions. Before the AIDS epidemic, the annual incidence of Kaposi's sarcoma in the United States was only 0.2 to 0.6 cases per million population, and only 32 individuals with disseminated MAC disease had been described in the medical literature (Safai. Ann NY Acad Sci 1984;437:373; Le Clair. Am Rev Respir Dis 1969;99:542; Masur. JAMA 1982;248:3013).

By the end of 1999, CDC had received reports of 166,368 HIV-infected patients in the United States with definitive diagnoses of PCP, 46,684 with definitive diagnoses of KS, and 41,873 with definitive diagnoses of disseminated MAC (personal communication).

In developing countries, patterns of both rare and endemic diseases have changed dramatically as HIV has spread, with a far greater toll now being exacted among the young and middle-aged, including well-educated members of the middle class.

In developing countries, the emergence of the HIV epidemic has dramatically changed patterns of disease in affected communities. As in developed countries, previously rare, "opportunistic" diseases such as PCP and certain forms of meningitis have become more commonplace. In addition, as HIV seroprevalence rates have risen, there have been significant increases in the burden of endemic conditions such as tuberculosis (TB), particularly among young people. For example, as HIV seroprevalence increased sharply in Blantyre, Malawi from 1986 to 1995, tuberculosis admissions at the city's main hospital rose more than 400 percent, with the largest increase in cases among children and young adults. In the rural Hlabisa District of South Africa, admissions to tuberculosis wards increased 360 percent from 1992 to 1998, concomitant with a steep rise in HIV seroprevalence. High rates of mortality due to endemic conditions such as TB, diarrheal diseases and wasting syndromes, formerly confined to the elderly and malnourished, are now common among HIV-infected young and middle-aged people in many developing countries (UNAIDS, 2000; Harries et al. Int J Tuberc Lung Dis 1997;1:346; Floyd et al. JAMA 1999;282:1087).

In studies conducted in both developing and developed countries, death rates are markedly higher among HIV-seropositive individuals than among HIV-seronegative individuals.

For example, Nunn and colleagues (BMJ 1997;315:767) assessed the impact of HIV infection over five years in a rural population in the Masaka District of Uganda. Among 8,833 individuals of all ages who had an unambiguous result on testing for HIV-antibodies (either 2 or 3 different test kits were used for blood samples from each individual), HIV-seropositive people were 16 times more likely to die over five years than HIV-seronegative people (see table). Among individuals ages 25 to 34, HIV-seropositive people were 27 times more likely to die than HIV-seronegative people.

In another study in Uganda, 19,983 adults in the rural Rakai District were followed for 10 to 30 months (Sewankambo et al. AIDS 2000;14:2391). In this cohort, HIV-seropositive people were 20 times more likely to die than HIV-seronegative people during 31,432 person-years of observation.

Similar findings have emerged from other studies (Boerma et al. AIDS 1998;12(suppl 1):S3); for example,

in Tanzania, HIV-seropositive people were 12.9 time more likely to die over two years than HIV-seronegative people (Borgdorff et al. Genitourin Med 1995;71:212)
in Malawi, mortality over three years among children who survived the first year of life was 9.5 times higher among HIV-seropositive children than among HIV-seronegative children (Taha et al. Pediatr Infect Dis J 1999;18:689)
in Rwanda, mortality was 21 times higher for HIV-seropositive children than for HIV-seronegative children after five years (Spira et al. Pediatrics 1999;14:e56). Among the mothers of these children, mortality was 9 times higher among HIV-seropositive women than among HIV-seronegative women in four years of follow-up (Leroy et al. J Acquir Immune Defic Syndr Hum Retrovirol 1995;9:415).
in Cote d'Ivoire, HIV-seropositive individuals with pulmonary tuberculosis (TB) were 17 times more likely to die within six months than HIV-seronegative individuals with pulmonary TB (Ackah et al. Lancet 1995; 345:607).
in the former Zaire (now the Democratic Republic of Congo), HIV-infected infants were 11 times more likely to die from diarrhea than uninfected infants (Thea et al. NEJM 1993;329:1696).
in South Africa, the death rate for children hospitalized with severe lower respiratory tract infections was 6.5 times higher for HIV-infected infants than for uninfected children (Madhi et al. Clin Infect Dis 2000;31:170).

Kilmarx and colleagues (Lancet 2000; 356:770) recently reported data on HIV infection and mortality in a cohort of female commercial sex workers in Chiang Rai, Thailand. Among 500 women enrolled in the study between 1991 and 1994, the mortality rate through October 1998 among women who were HIV-infected at enrollment (59 deaths among 160 HIV-infected women) was 52.7 times higher than among women who remained uninfected with HIV (2 deaths among 306 uninfected women). The mortality rate among women who became infected during the study (7 deaths among 34 seroconverting women) was 22.5 higher than among persistently uninfected women. Among the HIV-infected women, only 3 of whom received antiretroviral medications, all reported causes of death were associated with immunosuppression, whereas the reported causes of death of the two uninfected women were postpartum amniotic embolism and gunshot wound.

Excess mortality among HIV-seropositive people also has been repeatedly observed in studies in developed countries, perhaps most dramatically among hemophiliacs. For example, Darby et al. (Nature 1995;377:79) studied 6,278 hemophiliacs living in the United Kingdom during the period 1977-91. Among 2,448 individuals with severe hemophilia, the annual death rate was stable at 8 per 1,000 during 1977-84. While death rates remained stable at 8 per 1,000 from 1985-1992 among HIV-seronegative persons with severe hemophilia, deaths rose steeply among those who had become HIV-seropositive following HIV-tainted transfusions during 1979-1986, reaching 81 per 1,000 in 1991-92. Among 3,830 individuals with mild or moderate hemophilia, the pattern was similar, with an initial death rate of 4 per 1,000 in 1977-84 that remained stable among HIV-seronegative individuals but rose to 85 per 1,000 in 1991-92 among seropositive individuals.

Similar data have emerged from the Multicenter Hemophilia Cohort Study. Among 1,028 hemophiliacs followed for a median of 10.3 years, HIV-infected individuals (n=321) were 11 times more likely to die than HIV-negative subjects (n=707), with the dose of Factor VIII having no effect on survival in either group (Goedert. Lancet 1995;346:1425).

In the Multicenter AIDS Cohort Study (MACS), a 16-year study of 5,622 homosexual and bisexual men, 1,668 of 2,761 HIV-seropositive men have died (60 percent), 1,547 after a diagnosis of AIDS. In contrast, among 2,861 HIV-seronegative participants, only 66 men (2.3 percent) have died (A. Munoz, MACS, personal communication).

HIV can be detected in virtually everyone with AIDS.

Recently developed sensitive testing methods, including the polymerase chain reaction (PCR) and improved culture techniques, have enabled researchers to find HIV in patients with AIDS with few exceptions. HIV has been repeatedly isolated from the blood, semen and vaginal secretions of patients with AIDS, findings consistent with the epidemiologic data demonstrating AIDS transmission via sexual activity and contact with infected blood (Hammer et al. J Clin Microbiol 1993;31:2557; Jackson et al. J Clin Microbiol 1990;28:16).

Numerous studies of HIV-infected people have shown that high levels of infectious HIV, viral antigens, and HIV nucleic acids (DNA and RNA) in the body predict immune system deterioration and an increased risk for developing AIDS. Conversely, patients with low levels of virus have a much lower risk of developing AIDS.

For example, in an anlysis of 1,604 HIV-infected men in the Multicenter AIDS Cohort Study (MACS), the risk of a patient developing AIDS with six years was strongly associated with levels of HIV RNA in the plasma as measured by a sensitive test known as the branched-DNA signal-amplification assay (bDNA):

Plasma RNA concentration (copies/mL of blood)	Proportion of patients developing AIDS within six years
<500 501 - 3,000 3,001 - 10,000 10,001 - 30,000 >30,000	5.4% 16.6% 31.7% 55.2% 80.0%

(Source: Mellors et al. Ann Intern Med 1997;126:946)

Similar associations between increasing HIV RNA levels and a greater risk of disease progression have been observed in HIV-infected children in both developed and developing countries (Palumbo et al. JAMA 1998;279:756; Taha et al. AIDS 2000;14:453).

In the very small proportion of untreated HIV-infected individuals whose disease progresses very slowly, the amount of HIV in the blood and lymph nodes is significantly lower than in HIV-infected people whose disease progression is more typical (Pantaleo et al. NEJM 1995;332:209; Cao et al. NEJM 1995;332:201; Barker et al. Blood 1998;92:3105).

The availability of potent combinations of drugs that specifically block HIV replication has dramatically improved the prognosis for HIV-infected individuals. Such an effect would not be seen if HIV did not have a central role in causing AIDS.

Clinical trials have shown that potent three-drug combinations of anti-HIV drugs, known as highly active antiretroviral therapy (HAART), can significantly reduce the incidence of AIDS and death among HIV-infected individuals as compared to previously available HIV treatment regimens (Hammer et al. NEJM 1997;337:725; Cameron et al. Lancet 1998;351:543).

Use of these potent anti-HIV combination therapies has contributed to dramatic reductions in the incidence of AIDS and AIDS-related deaths in populations where these drugs are widely available, among both adults and children (Figure 1; CDC. HIV AIDS Surveillance Report 1999;11[2]:1; Palella et al. NEJM 1998;338:853; Mocroft et al. Lancet 1998;352:1725; Mocroft et al. Lancet 2000;356:291; Vittinghoff et al. J Infect Dis 1999;179:717; Detels et al. JAMA 1998;280:1497; de Martino et al. JAMA 2000;284:190; CASCADE Collaboration. Lancet 2000;355:1158; Hogg et al. CMAJ 1999;160:659; Schwarcz et al. Am J Epidemiol 2000;152:178; Kaplan et al. Clin Infect Dis 2000;30:S5; McNaghten et al. AIDS 1999;13:1687;).

For example, in a prospective study of more than 7,300 HIV-infected patients in 52 European outpatient clinics, the incidence of new AIDS-defining illnesses declined from 30.7 per 100 patient-years of observation in 1994 (before the availability of HAART) to 2.5 per 100 patient years in 1998, when the majority of patients received HAART (Mocroft et al. Lancet 2000;356:291).

Among HIV-infected patients who receive anti-HIV therapy, those whose viral loads are driven to low levels are much less likely to develop AIDS or die than patients who do not respond to therapy. Such an effect would not be seen if HIV did not have a central role in causing AIDS.

Clinical trials in both HIV-infected children and adults have demonstrated a link between a good virologic response to therapy (i.e. much less virus in the body) and a reduced risk of developing AIDS or dying (Montaner et al. AIDS 1998;12:F23; Palumbo et al. JAMA 1998;279:756; O'Brien et al. NEJM 1996;334:426; Katzenstein et al. NEJM 1996;335:1091; Marschner et al. J Infect Dis 1998;177:40; Hammer et al. NEJM 1997;337:725; Cameron et al. Lancet 1998;351:543).

This effect has also been seen in routine clinical practice. For example, in an analysis of 2,674 HIV-infected patients who started highly active antiretroviral therapy (HAART) in 1995-1998, 6.6 percent of patients who achieved and maintained undetectable viral loads (<400 copies/mL of blood) developed AIDS or died within 30 months, compared with 20.1 percent of patients who never achieved undetectable concentrations (Ledergerber et al. Lancet 1999;353:863).

Nearly everyone with AIDS has antibodies to HIV.

A survey of 230,179 AIDS patients in the United States revealed only 299 HIV-seronegative individuals. An evaluation of 172 of these 299 patients found 131 actually to be seropositive; an additional 34 died before their serostatus could be confirmed (Smith et al. N Engl J Med 1993;328:373).

Numerous serosurveys show that AIDS is common in populations where many individuals have HIV antibodies. Conversely, in populations with low seroprevalence of HIV antibodies, AIDS is extremely rare.

For example, in the southern African country of Zimbabwe (population 11.4 million), more than 25 percent of adults ages 15 to 49 are estimated to be HIV antibody-positive, based on numerous studies. As of November 1999, more than 74,000 cases of AIDS in Zimbabwe had been reported to the World Health Organization (WHO). In contrast, Madagascar, an island country off the southeast coast of Africa (population 15.1 million) with a very low HIV seroprevalence rate, reported only 37 cases of AIDS to WHO through November 1999. Yet, other sexually transmitted diseases, notably syphilis, are common in Madagascar, suggesting that conditions are ripe for the spread of HIV and AIDS if the virus becomes entrenched in that country (U.S. Census Bureau; UNAIDS, 2000; WHO. Wkly Epidemiol Rec 1999;74:1; Behets et al. Lancet 1996;347:831).

The specific immunologic profile that typifies AIDS - a persistently low CD4+ T-cell count - is extraordinarily rare in the absence of HIV infection or other known cause of immunosuppression.

For example, in the NIAID-supported Multicenter AIDS Cohort Study (MACS), 22,643 CD4+ T-cell determinations in 2,713 HIV-seronegative homosexual and bisexual men revealed only one individual with a CD4+ T-cell count persistently lower than 300 cells/mm³ of blood, and this individual was receiving immunosuppressive therapy. Similar results have been reported from other studies (Vermund et al. NEJM 1993;328:442; NIAID, 1995).

Newborn infants have no behavioral risk factors for AIDS, yet many children born to HIV-infected mothers have developed AIDS and died.

Only newborns who become HIV-infected before or during birth, during breastfeeding, or (rarely) following exposure to HIV-tainted blood or blood products after birth, go on to develop the profound immunosuppression that leads to AIDS. Babies who are not HIV-infected do not develop AIDS. In the United States, 8,718 cases of AIDS among children younger than age 13 had been reported to the CDC as of December 31, 1999. Cumulative U.S. AIDS deaths among individuals younger than age 15 numbered 5,044 through December 31, 1999. Globally, UNAIDS estimates that 480,000 child deaths due to AIDS occurred in 1999 alone (CDC. HIV/AIDS Surveillance Report 1999;11[2]:1; UNAIDS. AIDS epidemic update: June 2000).

Because many HIV-infected mothers abuse recreational drugs, some have argued that maternal drug use itself causes pediatric AIDS. However, studies have consistently shown that babies who are not HIV-infected do not develop AIDS, regardless of their mothers' drug use (European Collaborative Study. Lancet 1991;337:253; European Collaborative Study. Pediatr Infect Dis J 1997;16:1151; Abrams et al. Pediatrics 1995;96:451).

For example, a majority of the HIV-infected, pregnant women enrolled in the European Collaborative Study are current or former injection drug users. In this ongoing study, mothers and their babies are followed from birth in 10 centers in Europe. In a paper in Lancet, study investigators reported that none of 343 HIV-seronegative children born to HIV-seropositive mothers had developed AIDS or persistent immune deficiency. In contrast, among 64 seropositive children, 30 percent presented with AIDS within 6 months of age or with oral candidiasis followed rapidly by the onset of AIDS. By their first birthday, 17 percent died of HIV-related diseases (European Collaborative Study. Lancet 1991;337:253).

In a study in New York, investigators followed 84 HIV-infected and 248 HIV-uninfected infants, all born to HIV-seropositive mothers. The mothers of the two groups of infants were equally likely to be injection drug users (47 percent vs. 50 percent), and had similar rates of alcohol, tobacco, cocaine, heroin and methadone use. Of the 84 HIV-infected children, 22 died during a median follow-up period of 27.6 months, including 20 infants who died before their second birthday. Twenty-one of these deaths were classified as AIDS-related. Among the 248 uninfected children, only one death (due to child abuse) was reported during a median follow-up period of 26.1 months (Abrams et al. Pediatrics 1995;96:451).

The HIV-infected twin develops AIDS while the uninfected twin does not.

Because twins share an in utero environment and genetic relationships, similarities and differences between them can provide important insight into infectious diseases, including AIDS (Goedert. Acta Paediatr Supp 1997;421:56). Researchers have documented cases of HIV-infected mothers who have given birth to twins, one of whom is HIV-infected and the other not. The HIV-infected children developed AIDS, while the other children remained clinically and immunologically normal (Park et al. J Clin Microbiol 1987;25:1119; Menez-Bautista et al. Am J Dis Child 1986;140:678; Thomas et al. Pediatrics 1990;86:774; Young et al. Pediatr Infect Dis J 1990;9:454; Barlow and Mok. Arch Dis Child 1993;68:507; Guerrero Vazquez et al. An Esp Pediatr 1993;39:445).

Studies of transfusion-acquired AIDS cases have repeatedly led to the discovery of HIV in the patient as well as in the blood donor.

Numerous studies have shown an almost perfect correlation between the occurrence of AIDS in a blood recipient and donor, and evidence of homologous HIV strains in both the recipient and the donor (NIAID, 1995).

HIV is similar in genetic structure and morphology to other lentiviruses that often cause immunodeficiency in their animal hosts in addition to slow, progressive wasting disorders, neurodegeneration and death.

Like HIV in humans, animal viruses such as feline immunodeficiency virus (FIV) in cats, visna virus in sheep and simian immunodeficiency virus (SIV) in monkeys primarily infect cells of the immune system such as T cells and macrophages. For example, visna virus infects macrophages and causes a slowly progressive neurologic disease (Haase. Nature 1986;322:130).

HIV causes the death and dysfunction of CD4+ T lymphocytes in vitro and in vivo.

CD4+ T cell dysfunction and depletion are hallmarks of HIV disease. The recognition that HIV infects and destroys CD4+ T cells in vitro strongly suggests a direct link between HIV infection, CD4+ T cell depletion, and development of AIDS. A variety of mechanisms, both directly and indirectly related to HIV infection of CD4+ T cells, are likely responsible for the defects in CD4+ T cell function observed in HIV-infected people. Not only can HIV enter and kill CD4+ T cells directly, but several HIV gene products may interfere with the function of uninfected cells (NIAID, 1995; Pantaleo et al. NEJM 1993;328:327).

ANSWERING THE SKEPTICS:
RESPONSES TO ARGUMENTS THAT HIV DOES NOT CAUSE AIDS

MYTH: HIV antibody testing is unreliable.

FACT: Diagnosis of infection using antibody testing is one of the best-established concepts in medicine. HIV antibody tests exceed the performance of most other infectious disease tests in both sensitivity (the ability of the screening test to give a positive finding when the person tested truly has the disease ) and specificity (the ability of the test to give a negative finding when the subjects tested are free of the disease under study). Current HIV antibody tests have sensitivity and specificity in excess of 98% and are therefore extremely reliable (WHO, 1998; Sloand et al. JAMA 1991;266:2861).

Progress in testing methodology has also enabled detection of viral genetic material, antigens and the virus itself in body fluids and cells. While not widely used for routine testing due to high cost and requirements in laboratory equipment, these direct testing techniques have confirmed the validity of the antibody tests (Jackson et al. J Clin Microbiol 1990;28:16; Busch et al. NEJM 1991;325:1; Silvester et al. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8:411; Urassa et al. J Clin Virol 1999;14:25; Nkengasong et al. AIDS 1999;13:109; Samdal et al. Clin Diagn Virol 1996;7:55.

MYTH: There is no AIDS in Africa. AIDS is nothing more than a new name for old diseases.

FACT: The diseases that have come to be associated with AIDS in Africa - such as wasting syndrome, diarrheal diseases and TB - have long been severe burdens there. However, high rates of mortality from these diseases, formerly confined to the elderly and malnourished, are now common among HIV-infected young and middle-aged people, including well-educated members of the middle class (UNAIDS, 2000).

For example, in a study in Cote d'Ivoire, HIV-seropositive individuals with pulmonary tuberculosis (TB) were 17 times more likely to die within six months than HIV-seronegative individuals with pulmonary TB (Ackah et al. Lancet 1995; 345:607). In Malawi, mortality over three years among children who had received recommended childhood immunizations and who survived the first year of life was 9.5 times higher among HIV-seropositive children than among HIV-seronegative children. The leading causes of death were wasting and respiratory conditions (Taha et al. Pediatr Infect Dis J 1999;18:689). Elsewhere in Africa, findings are similar.

MYTH: HIV cannot be the cause of AIDS because researchers are unable to explain precisely how HIV destroys the immune system.

FACT: A great deal is known about the pathogenesis of HIV disease, even though important details remain to be elucidated. However, a complete understanding of the pathogenesis of a disease is not a prerequisite to knowing its cause. Most infectious agents have been associated with the disease they cause long before their pathogenic mechanisms have been discovered. Because research in pathogenesis is difficult when precise animal models are unavailable, the disease-causing mechanisms in many diseases, including tuberculosis and hepatitis B, are poorly understood. The critics' reasoning would lead to the conclusion that M. tuberculosis is not the cause of tuberculosis or that hepatitis B virus is not a cause of liver disease (Evans. Yale J Biol Med 1982;55:193).

MYTH: AZT and other antiretroviral drugs, not HIV, cause AIDS.

FACT: The vast majority of people with AIDS never received antiretroviral drugs, including those in developed countries prior to the licensure of AZT in 1987, and people in developing countries today where very few individuals have access to these medications (UNAIDS, 2000).

As with medications for any serious diseases, antiretroviral drugs can have toxic side effects. However, there is no evidence that antiretroviral drugs cause the severe immunosuppression that typifies AIDS, and abundant evidence that antiretroviral therapy, when used according to established guidelines, can improve the length and quality of life of HIV-infected individuals.

In the 1980s, clinical trials enrolling patients with AIDS found that AZT given as single-drug therapy conferred a modest (and short-lived) survival advantage compared to placebo. Among HIV-infected patients who had not yet developed AIDS, placebo-controlled trials found that AZT given as single-drug therapy delayed, for a year or two, the onset of AIDS-related illnesses. Significantly, long-term follow-up of these trials did not show a prolonged benefit of AZT, but also never indicated that the drug increased disease progression or mortality. The lack of excess AIDS cases and death in the AZT arms of these placebo-controlled trials effectively counters the argument that AZT causes AIDS (NIAID, 1995).

Subsequent clinical trials found that patients receiving two-drug combinations had up to 50 percent increases in time to progression to AIDS and in survival when compared to people receiving single-drug therapy. In more recent years, three-drug combination therapies have produced another 50 percent to 80 percent improvements in progression to AIDS and in survival when compared to two-drug regimens in clinical trials (HHS, 2004). Use of potent anti-HIV combination therapies has contributed to dramatic reductions in the incidence of AIDS and AIDS-related deaths in populations where these drugs are widely available, an effect which clearly would not be seen if antiretroviral drugs caused AIDS (Figure 1; CDC. HIV AIDS Surveillance Report 1999;11[2]:1; Palella et al. NEJM 1998;338:853; Mocroft et al. Lancet 1998;352:1725; Mocroft et al. Lancet 2000;356:291; Vittinghoff et al. J Infect Dis 1999;179:717; Detels et al. JAMA 1998;280:1497; de Martino et al. JAMA 2000;284:190; CASCADE Collaboration. Lancet 2000;355:1158; Hogg et al. CMAJ 1999;160:659; Schwarcz et al. Am J Epidemiol 2000;152:178; Kaplan et al. Clin Infect Dis 2000;30:S5; McNaghten et al. AIDS 1999;13:1687).

MYTH: Behavioral factors such as recreational drug use and multiple sexual partners account for AIDS.

FACT: The proposed behavioral causes of AIDS, such as multiple sexual partners and long-term recreational drug use, have existed for many years. The epidemic of AIDS, characterized by the occurrence of formerly rare opportunistic infections such as Pneumocystis carinii pneumonia (PCP) did not occur in the United States until a previously unknown human retrovirus - HIV - spread through certain communities (NIAID, 1995a; NIAID, 1995b).

Compelling evidence against the hypothesis that behavioral factors cause AIDS comes from recent studies that have followed cohorts of homosexual men for long periods of time and found that only HIV-seropositive men develop AIDS.

For example, in a prospectively studied cohort in Vancouver, 715 homosexual men were followed for a median of 8.6 years. Among 365 HIV-positive individuals, 136 developed AIDS. No AIDS-defining illnesses occurred among 350 seronegative men despite the fact that these men reported appreciable use of inhalable nitrites ("poppers") and other recreational drugs, and frequent receptive anal intercourse (Schechter et al. Lancet 1993;341:658).

Other studies show that among homosexual men and injection-drug users, the specific immune deficit that leads to AIDS - a progressive and sustained loss of CD4+ T cells - is extremely rare in the absence of other immunosuppressive conditions. For example, in the Multicenter AIDS Cohort Study, more than 22,000 T-cell determinations in 2,713 HIV-seronegative homosexual men revealed only one individual with a CD4+ T-cell count persistently lower than 300 cells/mm³ of blood, and this individual was receiving immunosuppressive therapy (Vermund et al. NEJM 1993;328:442).

In a survey of 229 HIV-seronegative injection-drug users in New York City, mean CD4+ T-cell counts of the group were consistently more than 1000 cells/mm³ of blood. Only two individuals had two CD4+ T-cell measurements of less than 300/mm³ of blood, one of whom died with cardiac disease and non-Hodgkin's lymphoma listed as the cause of death (Des Jarlais et al. J Acquir Immune Defic Syndr 1993;6:820).

MYTH: AIDS among transfusion recipients is due to underlying diseases that necessitated the transfusion, rather than to HIV.

FACT: This notion is contradicted by a report by the Transfusion Safety Study Group (TSSG), which compared HIV-negative and HIV-positive blood recipients who had been given transfusions for similar diseases. Approximately 3 years after the transfusion, the mean CD4+ T-cell count in 64 HIV-negative recipients was 850/mm³ of blood, while 111 HIV-seropositive individuals had average CD4+ T-cell counts of 375/mm³ of blood. By 1993, there were 37 cases of AIDS in the HIV-infected group, but not a single AIDS-defining illness in the HIV-seronegative transfusion recipients (Donegan et al. Ann Intern Med 1990;113:733; Cohen. Science 1994;266:1645).

MYTH: High usage of clotting factor concentrate, not HIV, leads to CD4+ T-cell depletion and AIDS in hemophiliacs.

FACT: This view is contradicted by many studies. For example, among HIV-seronegative patients with hemophilia A enrolled in the Transfusion Safety Study, no significant differences in CD4+ T-cell counts were noted between 79 patients with no or minimal factor treatment and 52 with the largest amount of lifetime treatments. Patients in both groups had CD4+ T cell-counts within the normal range (Hasset et al. Blood 1993;82:1351). In another report from the Transfusion Safety Study, no instances of AIDS-defining illnesses were seen among 402 HIV-seronegative hemophiliacs who had received factor therapy (Aledort et al. NEJM 1993;328:1128).

In a cohort in the United Kingdom, researchers matched 17 HIV-seropositive hemophiliacs with 17 HIV-seronegative hemophiliacs with regard to clotting factor concentrate usage over a ten-year period. During this time, 16 AIDS-defining clinical events occurred in 9 patients, all of whom were HIV-seropositive. No AIDS-defining illnesses occurred among the HIV-negative patients. In each pair, the mean CD4+ T cell count during follow-up was, on average, 500 cells/mm³ lower in the HIV-seropositive patient (Sabin et al. BMJ 1996;312:207).

Among HIV-infected hemophiliacs, Transfusion Safety Study investigators found that neither the purity nor the amount of Factor VIII therapy had a deleterious effect on CD4+ T cell counts (Gjerset et al., Blood 1994;84:1666). Similarly, the Multicenter Hemophilia Cohort Study found no association between the cumulative dose of plasma concentrate and incidence of AIDS among HIV-infected hemophiliacs (Goedert et al. NEJM 1989;321:1141.).

MYTH: The distribution of AIDS cases casts doubt on HIV as the cause. Viruses are not gender-specific, yet only a small proportion of AIDS cases are among women.

FACT: The distribution of AIDS cases, whether in the United States or elsewhere in the world, invariably mirrors the prevalence of HIV in a population. In the United States, HIV first appeared in populations of homosexual men and injection-drug users, a majority of whom are male. Because HIV is spread primarily through sex or by the exchange of HIV-contaminated needles during injection-drug use, it is not surprising that a majority of U.S. AIDS cases have occurred in men (U.S. Census Bureau, 1999; UNAIDS, 2000).

Increasingly, however, women in the United States are becoming HIV-infected, usually through the exchange of HIV-contaminated needles or sex with an HIV-infected male. The CDC estimates that 30 percent of new HIV infections in the United States in 1998 were in women. As the number of HIV-infected women has risen, so too has the number of female AIDS patients in the United States. Approximately 23 percent of U.S. adult/adolescent AIDS cases reported to the CDC in 1998 were among women. In 1998, AIDS was the fifth leading cause of death among women aged 25 to 44 in the United States, and the third leading cause of death among African-American women in that age group (NIAID Fact Sheet: HIV/AIDS Statistics).

In Africa, HIV was first recognized in sexually active heterosexuals, and AIDS cases in Africa have occurred at least as frequently in women as in men. Overall, the worldwide distribution of HIV infection and AIDS between men and women is approximately 1 to 1 (U.S. Census Bureau, 1999; UNAIDS, 2000).

MYTH: HIV cannot be the cause of AIDS because the body develops a vigorous antibody response to the virus.

FACT: This reasoning ignores numerous examples of viruses other than HIV that can be pathogenic after evidence of immunity appears. Measles virus may persist for years in brain cells, eventually causing a chronic neurologic disease despite the presence of antibodies. Viruses such as cytomegalovirus, herpes simplex and varicella zoster may be activated after years of latency even in the presence of abundant antibodies. In animals, viral relatives of HIV with long and variable latency periods, such as visna virus in sheep, cause central nervous system damage even after the production of antibodies (NIAID, 1995).

Also, HIV is well recognized as being able to mutate to avoid the ongoing immune response of the host (Levy. Microbiol Rev 1993;57:183).

MYTH: Only a small number of CD4+ T cells are infected by HIV, not enough to damage the immune system.

FACT: New techniques such as the polymerase chain reaction (PCR) have enabled scientists to demonstrate that a much larger proportion of CD4+ T cells are infected than previously realized, particularly in lymphoid tissues. Macrophages and other cell types are also infected with HIV and serve as reservoirs for the virus. Although the fraction of CD4+ T cells that is infected with HIV at any given time is never extremely high (only a small subset of activated cells serve as ideal targets of infection), several groups have shown that rapid cycles of death of infected cells and infection of new target cells occur throughout the course of disease (Richman J Clin Invest 2000;105:565).

MYTH: HIV is not the cause of AIDS because many individuals with HIV have not developed AIDS.

FACT: HIV disease has a prolonged and variable course. The median period of time between infection with HIV and the onset of clinically apparent disease is approximately 10 years in industrialized countries, according to prospective studies of homosexual men in which dates of seroconversion are known. Similar estimates of asymptomatic periods have been made for HIV-infected blood-transfusion recipients, injection-drug users and adult hemophiliacs (Alcabes et al. Epidemiol Rev 1993;15:303).

As with many diseases, a number of factors can influence the course of HIV disease. Factors such as age or genetic differences between individuals, the level of virulence of the individual strain of virus, as well as exogenous influences such as co-infection with other microbes may determine the rate and severity of HIV disease expression. Similarly, some people infected with hepatitis B, for example, show no symptoms or only jaundice and clear their infection, while others suffer disease ranging from chronic liver inflammation to cirrhosis and hepatocellular carcinoma. Co-factors probably also determine why some smokers develop lung cancer while others do not (Evans. Yale J Biol Med 1982;55:193; Levy. Microbiol Rev 1993;57:183; Fauci. Nature 1996;384:529).

MYTH: Some people have many symptoms associated with AIDS but do not have HIV infection.

FACT: Most AIDS symptoms result from the development of opportunistic infections and cancers associated with severe immunosuppression secondary to HIV.

However, immunosuppression has many other potential causes. Individuals who take glucocorticoids and/or immunosuppressive drugs to prevent transplant rejection or for autoimmune diseases can have increased susceptibility to unusual infections, as do individuals with certain genetic conditions, severe malnutrition and certain kinds of cancers. There is no evidence suggesting that the numbers of such cases have risen, while abundant epidemiologic evidence shows a staggering rise in cases of immunosuppression among individuals who share one characteristic: HIV infection (NIAID, 1995; UNAIDS, 2000).

MYTH: The spectrum of AIDS-related infections seen in different populations proves that AIDS is actually many diseases not caused by HIV.

FACT: The diseases associated with AIDS, such as PCP and Mycobacterium avium complex (MAC), are not caused by HIV but rather result from the immunosuppression caused by HIV disease. As the immune system of an HIV-infected individual weakens, he or she becomes susceptible to the particular viral, fungal and bacterial infections common in the community. For example, HIV-infected people in certain midwestern and mid-Atlantic regions are much more likely than people in New York City to develop histoplasmosis, which is caused by a fungus. A person in Africa is exposed to different pathogens than is an individual in an American city. Children may be exposed to different infectious agents than adults (USPHS/IDSA, 2001).

More information on this issue is available on the NIAID Focus On the HIV-AIDS Connection web page.

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

This article was created in 1994, last updated on February 27, 2003,
and posted to this Web site on September 26, 2005.

Ben Goldacre: The Doctor will sue you now

Eduard Grebe — Mon, 13 Apr 2009 16:08:56 +0000

This is an extract from Bad Science by Ben Goldacre, Published by Harper Perennial 2009. You are free to copy it, paste it, bake it, reprint it, read it aloud, as long as you don’t change it – including this bit – so that people know that they can find more ideas for free at www.badscience.net.

The Doctor Will Sue You Now

This chapter did not appear in the original edition of this book, because for fifteen months leading up to September 2008 the vitamin-pill entrepreneur Matthias Rath was suing me personally, and the Guardian, for libel. This strategy brought only mixed success. For all that nutritionists may fantasise in public that any critic is somehow a pawn of big pharma, in private they would do well to remember that, like many my age who work in the public sector, I don't own a flat. The Guardian generously paid for the lawyers, and in September 2008 Rath dropped his case, which had cost in excess of £500,000 to defend. Rath has paid £220,000 already, and the rest will hopefully follow. Nobody will ever repay me for the endless meetings, the time off work, or the days spent poring over tables filled with endlessly cross-referenced court documents.

On this last point there is, however, one small consolation, and I will spell it out as a cautionary tale: I now know more about Matthias Rath than almost any other person alive. My notes, references and witness statements, boxed up in the room where I am sitting right now, make a pile as tall as the man himself, and what I will write here is only a tiny fraction of the fuller story that is waiting to be told about him. This chapter, I should also mention, is available free online for anyone who wishes to see it.

Matthias Rath takes us rudely outside the contained, almost academic distance of this book. For the most part we've been interested in the intellectual and cultural consequences of bad science, the made-up facts in national newspapers, dubious academic practices in universities, some foolish pill-peddling, and so on. But what happens if we take these sleights of hand, these pill-marketing techniques, and transplant them out of our decadent Western context into a situation where things really matter?

In an ideal world this would be only a thought experiment. AIDS is the opposite of anecdote. Twenty-five million people have died from it already, three million in the last year alone, and 500,000 of those deaths were children. In South Africa it kills 300,000 people every year: that's eight hundred people every day, or one every two minutes. This one country has 6.3 million people who are HIV positive, including 30 per cent of all pregnant women. There are 1.2 million AIDS orphans under the age of seventeen. Most chillingly of all, this disaster has appeared suddenly, and while we were watching: in 1990, just 1 per cent of adults in South Africa were HIV positive. Ten years
later, the figure had risen to 25 per cent.

It's hard to mount an emotional response to raw numbers, but on one thing I think we would agree. If you were to walk into a situation with that much death, misery and disease, you would be very careful to make sure that you knew what you were talking about. For the reasons you are about to read, I suspect that Matthias Rath missed the mark.

This man, we should be clear, is our responsibility. Born and raised in Germany, Rath was the head of Cardiovascular Research at the Linus Pauling Institute in Palo Alto in California, and even then he had a tendency towards grand gestures, publishing a paper in the Journal of Orthomolecular Medicine in 1992 titled "A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of this Disease as a Cause for Human Mortality". The unified theory was high-dose vitamins.

He first developed a power base from sales in Europe, selling his pills with tactics that will be very familiar to you from the rest of this book, albeit slightly more aggressive. In the UK, his adverts claimed that "90 per cent of patients receiving chemotherapy for cancer die within months of starting treatment", and suggested that three million lives could be saved if cancer patients stopped being treated by conventional medicine. The pharmaceutical industry was deliberately letting people die for financial gain, he explained. Cancer treatments were "poisonous compounds" with "not even one effective treatment".

The decision to embark on treatment for cancer can be the most difficult that an individual or a family will ever take, representing a close balance between well-documented benefits and equally well-documented side-effects. Adverts like these might play especially strongly on your conscience if your mother has just lost all her hair to chemotherapy, for example, in the hope of staying alive just long enough to see your son speak.

There was some limited regulatory response in Europe, but it was generally as weak as that faced by the other characters in this book. The Advertising Standards Authority criticised one of his adverts in the UK, but that is essentially all they are able to do. Rath was ordered by a Berlin court to stop claiming that his vitamins could cure cancer, or face a €250,000 fine.

But sales were strong, and Matthias Rath still has many supporters in Europe, as you will shortly see. He walked into South Africa with all the acclaim, self-confidence and wealth he had amassed as a successful vitamin-pill entrepreneur in Europe and America, and began to take out full-page adverts in newspapers.

˜The answer to the AIDS epidemic is here," he proclaimed. Anti-retroviral drugs were poisonous, and a conspiracy to kill patients and make money. "Stop AIDS Genocide by the Drugs Cartel said one headline. "Why should South Africans continue to be poisoned with AZT? There is a natural answer to AIDS." The answer came in the form of vitamin pills. "Multivitamin treatment is more effective than any toxic AIDS drug. Multivitamins cut the risk of developing AIDS in half."

Rath's company ran clinics reflecting these ideas, and in 2005 he decided to run a trial of his vitamins in a township near Cape Town called Khayelitsha, giving his own formulation, VitaCell, to people with advanced AIDS. In 2008 this trial was declared illegal by the Cape High Court of South Africa. Although Rath says that none of his participants had been on anti-retroviral drugs, some relatives have given statements saying that they were, and were actively told to stop using them.

Tragically,Matthias Rath had taken these ideas to exactly the right place. Thabo Mbeki, the President of South Africa at the time, was well known as an "AIDS dissident", and to international horror, while people died at the rate of one every two minutes in his country, he gave credence and support to the claims of a small band of campaigners who variously claim that AIDS does not exist, that it is not caused by HIV, that anti-retroviral medication does more harm than good, and so on.

At various times during the peak of the AIDS epidemic in South Africa their government argued that HIV is not the cause of AIDS, and that anti-retroviral drugs are not useful for patients. They refused to roll out proper treatment programmes, they refused to accept free donations of drugs, and they refused to accept grant money from the Global Fund to buy drugs. One study estimates that if the South African national government had used anti-retroviral drugs for prevention and treatment at the same rate as the Western Cape province (which defied national policy on the issue), around 171,000 new HIV infections and 343,000 deaths could have been prevented between 1999 and 2007. Another study estimates that between 2000 and 2005 there were 330,000 unnecessary deaths, 2.2 million person years lost, and 35,000 babies unnecessarily born with HIV because of the failure to implement a cheap and simple mother-to-child-transmission prevention program. Between one and three doses of an ARV drug can reduce transmission dramatically. The cost is negligible. It was not available.

Interestingly, Matthias Rath's colleague and employee, a South African barrister named Anthony Brink, takes the credit for introducing Thabo Mbeki to many of these ideas. Brink stumbled on the "AIDS dissident" material in the mid-1990s, and after much surfing and reading, became convinced that it must be right. In 1999 he wrote an article about AZT in a Johannesburg newspaper titled "a medicine from hell". This led to a public exchange with a leading virologist. Brink contacted Mbeki, sending him copies of the debate, and was welcomed as an expert.

This is a chilling testament to the danger of elevating cranks by engaging with them. In his initial letter of motivation for employment to Matthias Rath, Brink described himself as "South Africa's leading AIDS dissident, best known for my whistle-blowing exposé of the toxicity and inefficacy of AIDS drugs, and for my political activism in this regard, which caused President Mbeki and Health Minister Dr Tshabalala-Msimang to repudiate the drugs in 1999″.

In 2000, the now infamous International AIDS Conference took place in Durban. Mbeki's presidential advisory panel beforehand was packed with "AIDS dissidents", including Peter Duesberg and David Rasnick. On the first day, Rasnick suggested that all HIV testing should be banned on principle, and that South Africa should stop screening supplies of blood for HIV. "If I had the power to outlaw the HIV antibody test," he said, "I would do it across the board." When African physicians gave testimony about the drastic change AIDS had caused in their clinics and hospitals, Rasnick said he had not seen "any evidence" of an AIDS catastrophe. The media were not allowed in, but one reporter from the Village Voice was present. Peter Duesberg, he said, "gave a presentation so removed from African medical reality that it left several local doctors shaking their heads". It wasn't AIDS that was killing babies and children, said the dissidents: it was the anti-retroviral medication.

President Mbeki sent a letter to world leaders comparing the struggle of the "AIDS dissidents" to the struggle against apartheid. The Washington Post described the reaction at the White House: "So stunned were some officials by the letter's tone and timing during final preparations for July's conference in Durban that at least two of them, according to diplomatic sources, felt obliged to check whether it was genuine. Hundreds of delegates walked out of Mbeki's address to the conference in disgust, but many more described themselves as dazed and confused. Over 5,000 researchers and activists around the world signed up to the Durban Declaration, a document that specifically addressed and repudiated the claims and concerns-at least the more moderate ones-of the "AIDS dissidents". Specifically, it addressed the charge that people were simply dying of poverty:

The evidence that AIDS is caused by HIV-1 or HIV-2 is clearcut, exhaustive and unambiguous... As with any other chronic infection, various co-factors play a role in determining the risk of disease. Persons who are malnourished, who already suffer other infections or who are older, tend to be more susceptible to the rapid development of AIDS following HIV infection. However, none of these factors weaken the scientific evidence that HIV is the sole cause of AIDS... Mother-to-child transmission can be reduced by half or more by short courses of antiviral drugs â€¦ What works best in one country may not be appropriate in another. But to tackle the disease, everyone must first understand that HIV is the enemy. Research, not myths, will lead to the development of more effective and cheaper treatments.

It did them no good. Until 2003 the South African government refused, as a matter of principle, to roll out proper antiretroviral medication programmes, and even then the process was half-hearted. This madness was only overturned after a massive campaign by grassroots organisations such as the Treatment Action Campaign, but even after the ANC cabinet voted to allow medication to be given, there was still resistance. In mid-2005, at least 85 per cent of HIV-positive people who needed anti-retroviral drugs were still refused them. That's around a million people.

This resistance, of course, went deeper than just one man; much of it came from Mbeki's Health Minister, Manto Tshabalala-Msimang. An ardent critic of medical drugs for HIV, she would cheerfully go on television to talk up their dangers, talk down their benefits, and became irritable and evasive when asked how many patients were receiving effective treatment. She declared in 2005 that she would not be "pressured" into meeting the target of three million patients on anti-retroviral medication, that people had ignored the importance of nutrition, and that she would continue to warn patients of the sideeffects of anti-retrovirals, saying: "We have been vindicated in
this regard. We are what we eat."

It's an eerily familiar catchphrase. Tshabalala-Msimang has also gone on record to praise the work of Matthias Rath, and refused to investigate his activities. Most joyfully of all, she is a staunch advocate of the kind of weekend glossy-magazine-style nutritionism that will by now be very familiar to you. The remedies she advocates for AIDS are beetroot, garlic, lemons and African potatoes. A fairly typical quote, from the Health Minister in a country where eight hundred people die every day from AIDS, is this: "Raw garlic and a skin of the lemon-not only do they give you a beautiful face and skin but they also protect you from disease." South Africa's stand at the 2006 World AIDS Conference in Toronto was described by delegates as the "salad stall". It consisted of some garlic, some beetroot, the African potato, and assorted other vegetables. Some boxes of anti-retroviral drugs were added later, but they were reportedly borrowed at the last minute from other conference delegates.

Alternative therapists like to suggest that their treatments and ideas have not been sufficiently researched. As you now know, this is often untrue, and in the case of the Health Minister's favoured vegetables, research had indeed been done, with results that were far from promising. Interviewed on SABC about this, Tshabalala-Msimang gave the kind of responses you'd expect to hear at any North London dinner-party discussion of alternative therapies.

First she was asked about work from the University of Stellenbosch which suggested that her chosen plant, the African potato, might be actively dangerous for people on AIDS drugs. One study on African potato in HIV had to be terminated prematurely, because the patients who received the plant extract developed severe bone-marrow suppression and a drop in their CD4 cell count-which is a bad thing-after eight weeks. On top of this, when extract from the same vegetable was given to cats with Feline Immunodeficiency Virus, they succumbed to full-blown Feline AIDS faster than their non-treated controls. African potato does not look like a good bet.

Tshabalala-Msimang disagreed: the researchers should go back to the drawing board, and "investigate properly". Why? Because HIV-positive people who used African potato had shown improvement, and they had said so themselves. If a person says he or she is feeling better, should this be disputed, she demanded to know, merely because it had not been proved scientifically? "When a person says she or he is feeling better, I must say 'No, I don't think you are feeling better'? I must rather go and do science on you'?" Asked whether there should be a scientific basis to her views, she replied: "Whose science?"

And there, perhaps, is a clue, if not exoneration. This is a continent that has been brutally exploited by the developed world, first by empire, and then by globalised capital. Conspiracy theories about AIDS and Western medicine are not entirely absurd in this context. The pharmaceutical industry has indeed been caught performing drug trials in Africa which would be impossible anywhere in the developed world. Many find it suspicious that black Africans seem to be the biggest victims of AIDS, and point to the biological warfare programmes set up by the apartheid governments; there have also been suspicions that the scientific discourse of HIV/AIDS might be a device, a Trojan horse for spreading even more exploitative Western political and economic agendas around a problem that is simply one of poverty.

And these are new countries, for which independence and self-rule are recent developments, which are struggling to find their commercial feet and true cultural identity after centuries of colonisation. Traditional medicine represents an important link with an autonomous past; besides which, anti-retroviral medications have been unnecessarily - offensively, absurdly - expensive, and until moves to challenge this became partially successful, many Africans were effectively denied access to medical treatment as a result.

It's very easy for us to feel smug, and to forget that we all have our own strange cultural idiosyncrasies which prevent us from taking up sensible public-health programmes. For examples, we don't even have to look as far as MMR. There is a good evidence base, for example, to show that needle-exchange programmes reduce the spread of HIV, but this strategy has been rejected time and again in favour of "Just say no." Development charities funded by US Christian groups refuse to engage with birth control, and any suggestion of abortion, even in countries where being in control of your own fertility could mean the difference between success and failure in life, is met with a cold, pious stare. These impractical moral principles are so deeply entrenched that Pepfar, the US Presidential Emergency Plan for AIDS Relief, has insisted that every recipient of international aid money must sign a declaration expressly promising not to have any involvement with sex workers.

We mustn't appear insensitive to the Christian value system, but it seems to me that engaging sex workers is almost the cornerstone of any effective AIDS policy: commercial sex is frequently the "vector of transmission", and sex workers a very high-risk population; but there are also more subtle issues at stake. If you secure the legal rights of prostitutes to be free from violence and discrimination, you empower them to demand universal condom use, and that way you can prevent HIV from being spread into the whole community. This is where science meets culture. But perhaps even to your own friends and neighbours, in whatever suburban idyll has become your home, the moral principle of abstinence from sex and drugs is more important than people dying of AIDS; and perhaps, then, they are no less irrational than Thabo Mbeki.

So this was the situation into which the vitamin-pill entrepreneur Matthias Rath inserted himself, prominently and expensively, with the wealth he had amassed from Europe and America, exploiting anti-colonial anxieties with no sense of irony, although he was a white man offering pills made in a factory abroad. His adverts and clinics were a tremendous success. He began to tout individual patients as evidence of the benefits that could come from vitamin pills - although in reality some of his most famous success stories have died of AIDS. When asked about the deaths of Rath's star patients, Health Minister Tshabalala-Msimang replied: "It doesn't necessarily mean that if I am taking antibiotics and I die, that I died of antibiotics."

She is not alone: South Africa's politicians have consistently refused to step in, Rath claims the support of the government, and its most senior figures have refused to distance themselves from his operations or to criticise his activities. Tshabalala-Msimang has gone on the record to state that the Rath Foundation "are not undermining the government's position. If anything, they are supporting it."

In 2005, exasperated by government inaction, a group of 199 leading medical practitioners in South Africa signed an open letter to the health authorities of the Western Cape, pleading for action on the Rath Foundation. "Our patients are being inundated with propaganda encouraging them to stop life-saving medicine," it said. "Many of us have had experiences with HIV infected patients who have had their health compromised by stopping their anti-retrovirals due to the activities of this Foundation." Rath's adverts continue unabated. He even claimed that his activities were endorsed by huge lists of sponsors and affiliates including the World Health Organization, UNICEF and UNAIDS. All have issued statements flatly denouncing his claims and activities. The man certainly has chutzpah.

His adverts are also rich with detailed scientific claims. It would be wrong of us to neglect the science in this story, so we should follow some through, specifically those which focused on a Harvard study in Tanzania. He described this research in full-page advertisements, some of which have appeared in the New York Times and the Herald Tribune. He refers to these paid adverts, I should mention, as if he had received flattering news coverage in the same papers. Anyway, this research showed that multivitamin supplements can be beneficial in a developing world population with AIDS: there's no problem with that result, and there are plenty of reasons to think that vitamins might have some benefit for a sick and frequently malnourished population.

The researchers enrolled 1,078 HIV-positive pregnant women and randomly assigned them to have either a vitamin supplement or placebo. Notice once again, if you will, that this is another large, well-conducted, publicly funded trial of vitamins, conducted by mainstream scientists, contrary to the claims of nutritionists that such studies do not exist. The women were followed up for several years, and at the end of the study, 25 per cent of those on vitamins were severely ill or dead, compared with 31 per cent of those on placebo. There was also a statistically significant benefit in CD4 cell count (a measure of HIV activity) and viral loads. These results were in no sense dramatic - and they cannot be compared to the demonstrable life-saving benefits of anti-retrovirals - but they did show that improved diet, or cheap generic vitamin pills, could represent a simple and relatively inexpensive way to marginally delay the need to start HIV medication in some patients.

In the hands of Rath, this study became evidence that vitamin pills are superior to medication in the treatment of HIV/AIDS, that anti-retroviral therapies "severely damage all cells in the body-including white blood cells", and worse, that they were "thereby not improving but rather worsening immune deficiencies and expanding the AIDS epidemic". The researchers from the Harvard School of Public Health were so horrified that they put together a press release setting out their support for medication, and stating starkly, with unambiguous clarity, that Matthias Rath had misrepresented their findings.

To outsiders the story is baffling and terrifying. The United Nations has condemned Rath's adverts as "wrong and misleading". "This guy is killing people by luring them with unrecognised treatment without any scientific evidence," said Eric Goemaere, head of Médecins sans Frontières SA, a man who pioneered anti-retroviral therapy in South Africa. Rath sued him.

It's not just MSF who Rath has gone after: he has also brought time-consuming, expensive, stalled or failed cases against a professor of AIDS research, critics in the media and others.

But his most heinous campaign has been against the Treatment Action Campaign. For many years this has been the key organisation campaigning for access to anti-retroviral medication in South Africa, and it has been fighting a war on four fronts. Firstly, TAC campaigns against its own government, trying to compel it to roll out treatment programmes for the population. Secondly, it fights against the pharmaceutical industry, which claims that it needs to charge full price for its products in developing countries in order to pay for research and development of new drugs - although, as we shall see, out of its $550 billion global annual revenue, the pharmaceutical industry spends twice as much on promotion and admin as it does on research and development. Thirdly, it is a grassroots organisation, made up largely of black women from townships who do important prevention and treatment-literacy work on the ground, ensuring that people know what is available, and how to protect themselves. Lastly, it fights against people who promote the type of information peddled by Matthias Rath and his ilk.

Rath has taken it upon himself to launch a massive campaign against this group. He distributes advertising material against them, saying "Treatment Action Campaign medicines are killing you" and "Stop AIDS genocide by the drug cartel", claiming-as you will guess by now-that there is an international conspiracy by pharmaceutical companies intent on prolonging the AIDS crisis in the interests of their own profits by giving medication that makes people worse. TAC must be a part of this, goes the reasoning, because it criticises Matthias Rath. Just like me writing on Patrick Holford or Gillian McKeith, TAC is perfectly in favour of good diet and nutrition. But in Rath's promotional literature it is a front for the pharmaceutical industry, a "Trojan horse" and a "running dog". TAC has made a full disclosure of its funding and activities, showing no such connection: Rath presented no evidence to the contrary, and has even lost a court case over the issue, but will not let it lie. In fact he presents the loss of this court case as if it was a victory.

The founder of TAC is a man called Zackie Achmat, and he is the closest thing I have to a hero. He is South African, and coloured, by the nomenclature of the apartheid system in which he grew up. At the age of fourteen he tried to burn down his school, and you might have done the same in similar circumstances. He has been arrested and imprisoned under South Africa's violent, brutal white regime, with all that entailed. He is also gay, and HIV-positive, and he refused to take anti-retroviral medication until it was widely available to all on the public health system, even when he was dying of AIDS, even when he was personally implored to save himself by Nelson Mandela, a public supporter of anti-retroviral medication and Achmat's work.

And now, at last, we come to the lowest point of this whole story, not merely for Matthias Rath's movement, but for the alternative therapy movement around the world as a whole. In 2007, with a huge public flourish, to great media coverage, Rath's former employee Anthony Brink filed a formal complaint against Zackie Achmat, the head of the TAC. Bizarrely, he filed this complaint with the International Criminal
Court at The Hague, accusing Achmat of genocide for successfully campaigning to get access to HIV drugs for the people of South Africa.

It's hard to explain just how influential the "AIDS dissidents" are in South Africa. Brink is a barrister, a man with important friends, and his accusations were reported in the national news media -and in some corners of the Western gay press-as a serious news story. I do not believe that any one of those journalists who reported on it can possibly have read Brink's indictment to the end.

I have.

The first fifty-seven pages present familiar anti-medication and "AIDS-dissident" material. But then, on page fifty-eight, this "indictment" document suddenly deteriorates into something altogether more vicious and unhinged, as Brink sets out what he believes would be an appropriate punishment for Zackie. Because I do not wish to be accused of selective editing, I will now reproduce for you that entire section, unedited, so you can see and feel it for yourself.

The document was described by the Rath Foundation as "entirely valid and long overdue".

This story isn't about Matthias Rath, or Anthony Brink, or Zackie Achmat, or even South Africa. It is about the culture of how ideas work, and how that can break down. Doctors criticise other doctors, academics criticise academics, politicians criticise politicians: that's normal and healthy, it's how ideas improve. Matthias Rath is an alternative therapist, made in Europe. He is every bit the same as the British operators that we have seen in this book. He is from their world.

Despite the extremes of this case, not one single alternative therapist or nutritionist, anywhere in the world, has stood up to criticise any single aspect of the activities of Matthias Rath and his colleagues. In fact, far from it: he continues to be fêted to this day. I have sat in true astonishment and watched leading figures of the UK's alternative therapy movement applaud Matthias Rath at a public lecture (I have it on video, just in case there's any doubt). Natural health organisations continue to defend Rath. Homeopaths' mailouts continue to promote his work. The British Association of Nutritional Therapists has been invited to comment by bloggers, but declined. Most, when challenged, will dissemble."Oh," they say, "I don't really know much about it." Not one person will step forward and dissent.

The alternative therapy movement as a whole has demonstrated itself to be so dangerously, systemically incapable of critical self-appraisal that it cannot step up even in a case like that of Rath: in that count I include tens of thousands of practitioners, writers, administrators and more. This is how ideas go badly wrong. In the conclusion to this book, written before I was able to include this chapter, I will argue that the biggest dangers posed by the material we have covered are cultural and intellectual.

I may be mistaken.

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Thabo Mbeki, HIV/AIDS and bogus scientific controversies

Eduard Grebe — Mon, 23 Mar 2009 20:28:38 +0000

by Martin Weinel (Originally published on Politicsweb.)

Almost every day governments around the world have to make political decisions that depend on scientific or technical knowledge. Where and how to store nuclear waste? How to respond to global climate change? Should a particular medicine be made freely available to the whole population or should its use be highly restricted or even banned? These and countless other 'science policy decisions' show that policy making is highly dependent on scientific knowledge.

The difficulty, however, is knowing how much weight to give to scientific knowledge. In some cases this appears straightforward. For example, there is a scientific consensus that prolonged exposure to high doses of radiation from nuclear waste is lethal for human beings. Thus, if somebody suggests storing nuclear waste in cardboard boxes in down-town Johannesburg, the suggestion would be immediately rejected based on our knowledge of the effects of radiation. In other cases, particularly those where people with specialist knowledge - i.e. the experts - disagree about scientific issues it is not so easy. For example, there is disagreement between experts about whether cross-fertilisation between genetically modified crops (GM crops) and unmodified crops represents a real risk and if it does, which measures are most suited to prevent cross-fertilisation. As such, although no-one can point to conclusive scientific evidence that shows cross-fertilisation will occur, critics of GM crops can point to the uncertainties behind the claims of GM proponents and by doing so urge policy-makers to adopt a precautionary approach.

Put another way, it seems that a scientific consensus should constrain policy makers more tightly than a scientific controversy. In the case of radioactive waste, the scientific consensus means that, if it has to be stored, then it should be stored in containers that reduce the emission of radiation as far as possible and in places that offer protection from radiation should the containers be damaged. This is not to say these constraints fully determine the policy but to acknowledge that they do set some limits within which policy makers must work. For example, while safe storage might be theoretically feasible, policy-makers might choose to abstain from using nuclear power altogether.

If there is no consensus amongst the experts then the effect of scientific knowledge is less powerful and political judgement more important. If it is unclear whether genetically modified crops do cross-fertilise with unmodified plants then a decision to introduce GM crops carries an unknown risk of affecting bio-diversity. Policy makers can either choose to accept this risk, perhaps pointing to some other benefits, or they can decide not to allow GM crops to be planted. Both positions fit with at least some of the available evidence and, because both sides in the argument have at least some scientific credibility, neither puts a binding constraint on the policy debate.

The observation that scientific controversies create a space that scientific consensus effectively closes down has not been lost on political strategists, campaigners and lobby groups. During his presidency, George W. Bush famously abstained from acting on climate change by referring to a controversy among scientists about the causal role of humans. Frank Luntz, a Republican pollster, made the rationale behind this stance explicit when he was quoted in an editorial of the New York Times on 15 March 2003:

Should the public come to believe that the scientific issues are settled' their views about global warming will change accordingly. Therefore, you need to continue to make the lack of scientific certainty a primary issue.

The question is whether or not the Bush administration was correct to invoke scientific uncertainty in this way. If there is a genuine scientific controversy then allowing a greater role for political judgements is the correct way to proceed. But what if there is a consensus within the scientific community and the policy makers create the impression of a controversy in order to delay or avoid a decision. In this case, it would seem odd to allow such an inauthentic scientific controversy to have a powerful effect on policy.

But how can we tell whether a controversy is authentic or not? If we define a genuine controversy as one that the relevant scientific community would accept as real then an inauthentic scientific controversy is one in which the degree of publicly invoked disagreement does not represent genuine uncertainty within the community of relevant experts. In the case of global climate change, we can see that even though science of global climate change is beset with many uncertainties, the International Panel on Climate Change (IPCC) - probably the most authoritative and representative expert institution on question of climate change - has unequivocally endorsed the view that human use of fossil fuels is at least partly to blame for the change in climate patterns that is observable around the globe. This is not to say that what these experts say is true or right - they might be wrong - but their advice is the best scientific advice that we got on this matter and that, at this moment, it tells us that anthropogenic climate change is happening. Politicians should take this into account in deciding on their actions.

Another example of such an 'inauthentic scientific controversy', although arguably less strategically inspired, was observable in South Africa a few years ago: the 'controversy' about the safety of AZT when used to reduce the risk of mother-to-child transmission of HIV.

On 28 October 1999, President Thabo Mbeki told the members of the National Council of Provinces:

Two matters in this regard [the demand to make AZT available in the public health service] have been brought to our attention.

One of these is that there are legal cases pending in this country, the United Kingdom and the United States against AZT on the basis that this drug is harmful to health.

There also exists a large volume of scientific literature alleging that, among other things, the toxicity of this drug is such that it is in fact a danger to health. These are matters of great concern to the Government as it would be irresponsible for us not to heed the dire warnings which medical researchers have been making.

I have therefore asked the Minister of Health, as a matter of urgency, to go into all these matters so that, to the extent that is possible, we ourselves, including our country's medical authorities, are certain of where the truth lies.

To understand this matter better, I would urge the Honourable Members of the National Council to access the huge volume of literature on this matter available on the Internet, so that all of us can approach this issue from the same base of information.

Apparently the first argument, related to pending legal cases, turned out to be wrong. But President Mbeki obviously did not believe that this was a strong argument in any case as he only mentioned it briefly and it never appeared again in his public speeches. The second argument is much more elaborated and represented one of government's main arguments against the introduction of AZT (or Nevirapine for that matter as the Minister of Health, Tshabalala-Msimang, would tell Parliament in a statement on 16 November 1999). In this case, the idea of a scientific controversy is invoked when President Mbeki claims that 'a large volume of scientific literature' exists which alleges that AZT is so toxic that it is a 'danger to health' and not, as one of its proponents put it, a 'medicine from heaven'. The contributors to this body of literature were apparently 'medical researchers'.

Identifying this as an inauthentic controversy requires more work but can be done. The initial problem is that President Mbeki is acting, so it seems, merely as a journalist: he just reports or describes what some medical researchers are saying in order to bring it to the attention of the government and the medical authorities in South Africa.

The reason why this also counts as an inauthentic scientific controversy is that President Mbeki is not, in fact, acting as a reporter; instead, he acts as a creator of the controversy. The revealing statement is found in the last paragraph of the above quote when the President urges the Members of the National Council to lift themselves up to the same level of understanding by 'accessing' - and presumably reading - the 'large volume of literature on this matter on the Internet' for themselves. Whether Mbeki really found the literature he was referring to on the Internet or whether it was given to him by people such as Anthony Brink, Anita Allen or Zigi Visser does not really matter. What matters is that the President's knowledge about AZT comes not from the scientific community itself but from reading the scientific literature. By forming a judgement on AZT, he has to rely on his own expertise on the matter, which is insufficient, as I will argue below.

President Mbeki confirmed that he was reading the scientific literature on his own in the welcome speech to members of the Presidential Advisory Panel on AIDS in May 2000 when he reflected on how he started to immerse himself into the scientific literature (which he probably did wholeheartedly only after his speech in late October):

[...] I faced this difficult problem of reading all these complicated things that you scientists write about, in this language I don't understand. So I ploughed through lots and lots of documentation, with dictionaries all around me in case there were words that seemed difficult to understand. I would phone the Minister of Health [who holds a couple of degrees in health-related disciplines] and say, 'Minister, what does this word mean?' And she would explain.

So what exactly is the problem with accessing scientific literature on your own and reading it? While President Mbeki's effort to read scientific literature himself is admirable, the decisive question is how reliable are the conclusions that can be reached solely from reading the academic literature.

Perhaps surprisingly, it is entirely wrong to assume reading alone can give you enough specialist knowledge - expertise - to intervene on a scientific matter. The problem is not so much to understand the content of scientific papers: well written scientific papers can be unexpectedly accessible and simply reading the abstract might sometimes be enough for even the uninitiated to gain a rough but sufficient understanding of what the paper is about. The real problems start, however, when it comes to judging the credibility of a paper and its relative importance to a scientific field. While to the outsider journal articles and books - written material in short - might seem to embody the essence of science, science is predominantly an oral culture. The publication of results is important but it is only the first hurdle. Having them read and believed is even more important but this attribution of credibility and importance is much harder to outsiders to pick up as it takes place in the personal encounters between scientists at conferences, workshops and other meetings. Other markers of credibility, which do not necessary involve face-to-face contact, but which nevertheless presuppose familiarity with the field, include the prestige of a lab, a research group or institution, the standing and reputation of the co-authors and the methodological assumptions and techniques that are conventionally used in different settings.

In short, to know which papers and results to trust and to judge their relative importance in a scientific field, one needs to immerse oneself into the 'culture' of a particular scientific community. Without immersion an isolated reader simply lacks the necessary, often tacit, knowledge needed to know what to read and whom to trust.

In the case of AZT, President Mbeki never immersed himself in the community of experts on anti-retroviral drugs and prevention of mother-to-child transmission of HIV. Instead he assumed that reading alone gave him enough expertise to declare AZT a 'danger to health'. President Mbeki created an inauthentic scientific controversy by referring to the 'warnings of medical researchers' as this gave the impression that a scientific controversy about the safety of AZT was ongoing and that no scientific consensus constrained the policy options of the government. While any positive claim can be challenged if enough effort is made, it remains that for all practical purposes it was a 'certainty' in 1999 (and is still one today) that the benefits of anti-retrovirals in their use to prevent mother-to-child transmission largely outweighed the existent risks. By relying on the reading of scientific literature to make a judgement about AZT's safety, President Mbeki made a mistake.

Had the President done what politicians usually do when they are confronted with technical matters that are well beyond their own expertise -seeking the advice of experts on the matter - he would have discovered at least two things. First, he would have learned that the vast majority of scientists with expertise on AZT and other anti-retroviral drugs shared the view that the benefits of anti-retroviral drugs largely outweigh the risks when it comes to the prevention of mother-to-child transmission. In this regard, the composition of Presidential Advisory Panel on AIDS, which was established in May 2000, did not even approximately reflect the opinion within the scientific community. As a leading South African scientist told me last year:

Out of the 33 people on the panel about 16 of them were dissidents [people who do not believe that HIV causes AIDS and/or that anti-retroviral drugs have some therapeutic effect], which is about the sum-total, the grand sample of dissidence, this is the census, and then the 16 scientists were a small sample from across the globe.

Second, had President Mbeki asked experts directly he would also have learned more about those he had apparently chosen to trust as reflected, again, by the composition of the AIDS Advisory Panel. He would have learned, for example, that they not only represented a very tiny minority as the above quote shows, but also that some of them had hardly any direct expertise of anti-retrovirals or HIV/AIDS. He would also have learnt that their credibility within the expert community was very low and that this was not because the scientific mainstream feared their theories like the church feared the theories of Galileo, but rather because their theories had been shown to be wrong on many occasions.

The consequences of Mbeki's mistake were grave. By creating an 'inauthentic scientific controversy' and delaying the introduction of a widely supported policy, Mbeki's actions have led, according to recent estimates, to the unnecessary infection of about 35,000 babies with HIV in South Africa between 2000 and 2005 (Chigwedere et al. 2008, see also Nattrass 2008).

This shows that inauthentic scientific controversies can have devastating effects. It is for this reason, if not other, that recognising such controversies and preventing them from influencing policy-making matters.

References

Chigwedere, Pride et al. (2008) 'Estimating the lost benefits of antiretroviral drug use in South Africa', Journal of Acquired Immune Deficit Syndrome 49(4): 410-415. <http://www.harvardscience.harvard.edu/medicine-health/articles/south-african-aids-policy-tied-330000-lives-lost>

Nattrass, Nicoli (2008) 'AIDS and the scientific governance of medicine in post-apartheid South Africa', African Affairs 107(427): 157-176. <http://afraf.oxfordjournals.org/cgi/content/abstract/107/427/157>

"With the stroke of a pen" – Andrew Maniotis's bizarre email to the Gates Foundation

AIDSTruth — Sat, 07 Feb 2009 17:12:09 +0000

Sometimes AIDS denialists do such a good job of discrediting themselves that we don't have to do much to counter them. See this email from Andy Maniotis to the Bill and Melinda Gates Foundation, with an attached document that he claims to have also sent to President Obama (while offering to serve as Mark Dybul's replacement).

From: Andy Maniotis [redacted]

Date: Fri, 6 Feb 2009 12:21:38 -0600
To: [redacted]
Subject: With the stroke of a pen

Dear Mr. or Mrs. Gates,

I am deeply concerned about the information you have been receiving regarding the scientific basis upon which several of your global policies are based.

Mr. Dybul, Mr. Bush's World AIDS coordinator has just been fired. In a letter to President Obama's team, I have offerred to serve as his replacement.

I would appreciate you forwarding the three short documents to Mr. Gates, or to Mrs. Gates, because I believe they deserve to have complete information regarding several of the assumptions your organization is pursuing. Mr. Gates releasing mosquitos yesterday to make his valid point illustrates to me the depth and sincerity of his vision, and the extent to which he is willing to "wake people up." Malaria-one of Man's greatest diseases, was once thought to be caused by "bad air" thus its name. I am suggesting that you will find that several current "plagues" will be found to be based on different mechanisms which suggest different strategies, instead of pursuing supernatural beings in the case of certain viral diseases, and the universally failed approaches to vanquish them.

I hope these documents will serve a similar purpose as releasing mosquitoes on a Western audience: I hope that like the mosquitoes, the following information will cause some concern for alarm as well.

With much thanks in this important matter,

Sincerely,

Andrew Maniotis, Ph.D.
Visiting Associate Professor of Bioengineering: Program of tumor mechanics and tissue regeneration;
212 SEO, MC 063
University of Illinois at Chicago, Chicago, IL 60607
Secure Email: [redacted]
University Email: [redacted]
Cell: [redacted]

Attachment	Size
with the stroke of a pen.pdf	485.02 KB

AIDSTruth.org - Features

Quackery taken to task

The Price of Denial: A documentary on the legacy of AIDS denialism in South Africa

View Part I:

View Part II

New myth debunked: The fact that some HIV-positive people live in good health without treatment for many years proves that HIV is harmless

In Memoriam, Lambros Papantoniou

Rian Malan still getting AIDS stats wrong

Constantine and Weiss pinpoint misrepresentations

Statements by Professor Niel Constantine and Professor Robin Weiss about the Misrepresentation of their Interviews in “House of Numbers.”

Dr. Constantine's Statement

Dr. Weiss's Statement

Science, pseudoscience and professional responsibility

The Shameless Rian Malan

AIDS and mortality in South Africa

References

How to spot an AIDS denialist

Warning about pseudo-scientific review of alternative AIDS medicines

Anthony Mbewu is made director of GFHR: Is this an appropriate appointment?

References

"House of Numbers" Lies about Research Findings on T Cells Destruction and AIDS

Notes

Maggiore's labs

South Africa needs an HIV/AIDS truth commission

Preventable deaths

Call for a commission

Reviled, Yes. Genius? Not So Much.

Newsweek Exposes Duesberg’s Psychopathology

Endnotes

Real Answers to the Fake Questions in “House of Numbers”

“House of Numbers” asks if there is really a scientific consensus about HIV/AIDS.

“House of Numbers” questions the reliability of the HIV test. Does the HIV antibody test actually tell us anything at all?

“House of Numbers” questions the practice of asking about risk factors in testing and diagnosis. Don’t doctors just want to know if you are gay or a drug user, and isn’t the diagnosis really bogus?

“House of Numbers” questions why some people who are exposed to HIV are not infected. Maybe HIV isn’t communicable? Maybe it doesn’t exist?

“House of Numbers” questions how one disease varies so much in different people. Could it be that there’s no such disease as AIDS?

“House of Numbers” asks if a disease that is diagnosed differently on different continents is really only one disease.

“House of Numbers” asks if the profits that pharmaceutical companies make from HIV drugs might in fact be the reason for the invention of HIV/AIDS.

David Rasnick fails to declare conflict of interests

References:

New myth debunked: HIV is an endogenous retrovirus

Fact: HIV has been shown to be exogenous throughout 20+ years of research.

Early evidence:

Southern Blots:

PCR:

The Genome Projects:

Common Sense:

References

Justice After AIDS Denialism: Should There Be Prosecutions and Compensation?

Clarification on false claims made in emails circulating on the Internet

Clark Baker - Ex-cop and homophobic right-wing blogger

A historical reflection on the discovery of human retroviruses

Abstract

Background

Paving the way for the discovery of HIV

The discovery of the first human retrovirus

The isolation of what is now called HIV-1 (will also be referred to as HIV, LAV, IDAV-1, IDAV-2, LAV-1, HTLV-III and ARV) and the demonstration of this virus as the cause of AIDS

The LAV/HTLV-IIIB contamination story and the patent feud between the Pasteur Institute and NIH

Conclusion

References

The dangers of denying HIV: John Moore reviews Seth Kalichman's Denying AIDS in Nature

Denying AIDS: Conspiracy Theories, Pseudoscience, and Human Tragedy

'House of Numbers' is an AIDS denialist propaganda film

NIAID: The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome

Introduction

The Definition of AIDS

The Designation AIDS is a Surveillance Tool

Quantifying the Epidemic

A Brief History of the Emergence of AIDS

Initial Theories

Retrovirus Hypothesis

Seroprevalence Surveys

HIV and Other Lentiviruses

Table 1. Lentiviruses

Virus

Host

Primary cell type

Clinical disorder

Course of HIV Infection

Immunologic Profile of People With AIDS

Mechanisms of CD4+ T Cell Depletion

Number in analysis
ZDV/imm/ P/def

No. progressingto AIDS or death
ZDV/imm/P/def

Number in analysis
ZDV/imm/ P/def

No. progressingto AIDS or death
ZDV/imm/P/def

ANSWERING THE SKEPTICS:
RESPONSES TO ARGUMENTS THAT HIV DOES NOT CAUSE AIDS