AIDS & HIV?

Does HIV cause AIDS? Is AIDS a single disease? Do anti-viral drugs really help? Dr. Mae-Wan Ho investigates

“HIV is not the cause of AIDS”

Peter Duesberg was, and still is, professor of molecular biology at the University of California at Berkeley, member of the National Academy of Sciences and recipient of a 1985 Outstanding Investigative Grant from the National Institutes of Health. He was tipped as a Nobel candidate for his work on viral oncogenes (genes causing cancer).

But all that came to a crashing end in 1987, when he published a paper [1] claiming that HIV did not cause AIDS, contrary to what the scientific community had come to believe to this day (Box 1), but was instead the result of drug use. He soon lost all his research grants, but that has not silenced him.

Ironically, Duesberg’s hypothesis was generally held before the idea that HIV caused AIDS became accepted (see Box 2).

Within a few years of Duesberg’s paper, HIV-negative AIDS cases began to turn up, and people started to take notice of his theory, which has been refined over the years together with his colleague David Rasnick and others.

In a hefty review published in June 2003, Duesberg and Rasnick, together with Claus Koehnlein from Kiel, Germany [2] presented a long list of questions (“paradoxes”) that the HIV-AIDS hypothesis cannot answer, or at least not satisfactorily according to the usual understanding of a viral disease.

One major difficulty that AIDS dissidents have with the HIV-AIDS hypothesis is that the HIV virus is very unusual. It cannot readily be isolated from the AIDS patients. The ‘viral load’ measured in patients refers, not to actual virus present, but to the amount of viral DNA fragments that can be amplified by PCR from the RNA of a rare virus or of DNA of rare latently infected cells from the patient.

But defenders of the HIV-AIDS hypothesis have no difficulty at all in acknowledging that HIV is a strange new virus that can remain latent for years, being held in check by the body’s immune system, which, nevertheless finally succumbs to the virus (see “Can exercise help AIDS?” this series).

The most contentious of Duesberg’s claim is that AIDS is not contagious, and not sexually transmitted. That, his infuriated critics say, is simply to encourage people to have unprotected sex, and to use dirty needles for injecting drugs, both of which would expose them to high risks of infection with HIV and a host of other disease agents besides. Yet, that is perhaps the single point on which Duesberg and Rasnick are most adamant. Rasnick has stated categorically, “I want to stress that AIDS is not contagious, sexually transmitted or caused by HIV or any other virus.” And he is able to cite at least as many papers to support his thesis as his opponents can to refute him.

“HIV does not cause AIDS, it is just a harmless passenger virus,” that’s the claim of Duesberg and colleagues. The WHO (World Health Organization) estimates that 34.3 million are HIV-positive worldwide in 2000, yet only 1.4% developed AIDS. Similarly, in 1985, only 1.2% of the 1 million US citizens with HIV developed AIDS.

Defenders of HIV-AIDS hypothesis will readily admit that the progression from HIV infection to AIDS disease may indeed take years, though it will almost invariably happen.

Like all passenger viruses, it is inherited, i.e., transmitted from mother to offspring, but is not infectious. AIDS disease in infants and children, Duesberg and Rasnick claim, results from prenatal consumption of recreational and anti-HIV drugs by unborn babies through their mothers. That too is a very contentious claim.

Duesberg and colleagues charge that, “the HIV-AIDS hypothesis has remained entirely unproductive” to this day. There is as yet no anti-HIV-AIDS vaccine, no effective prevention and not a single AIDS patient has ever been cured. Those are “the hallmarks of a flawed hypothesis”.

A much more productive hypothesis, they say, is that AIDS is a collection of chemical epidemics, caused by recreational drugs, anti-HIV drugs, and malnutrition.

The Durban Declaration

Duesberg is by no means a lone voice. A growing number of “AIDS dissidents” within the scientific community posed such a threat to the establishment that a remarkable “Durban Declaration” was made in Durban, South Africa, as thousands were about to gather for the 13^th International AIDS Conference in July 2000. The Declaration began: “HIV causes AIDS. Curbing the spread of this virus must remain the first step towards eliminating this devastating disease”

The Declaration, published in Nature [3], was signed by over 5 000, including Nobel prizewinner, directors of leading research institution, scientific academies and medical societies, such as US national Academy of Sciences, Max Planck Institutes, the Pasteur Institute in Paris, the Royal Society of London, the AIDS society of India and the National Institute of Virology in South Africa.

At the time, President Mbeki of South Africa had assembled a Presidential AIDS Advisory Panel, which included Duesberg and Rasnick among other AIDS dissidents, together with many scientists holding the conventional view. Duesberg and Rasnick were among the 11 co-authors who signed a rebuttal to the Durban Declaration, published in Nature correspondence [4], stating that they “reject as outrageous” the attempt to outlaw open discussion of alternative viewpoints; it was an act of intolerance “which has no place in any branch of science.”

The full report of the Presidential AIDS Advisory Panel published a year later [5] makes fascinating reading. It is the best summary of the rather complex debate over all aspects of AIDS, from causation to therapy. Unfortunately, none of the scientific papers cited by the panel members during the debate was included in the report.

AIDS is a collection of disparate diseases

The starting point to this controversy is the disparate nature of the diseases that have been lumped together as AIDS. Even a staunch defender of the HIV-AIDS hypothesis, Helene Gayle, then director of the US Centers for Disease Control’s National Center of HIV, STD a nd TB Prevention, and now director Bill and Melinda Gates Foundation’s HIV, TB and Reproductive Health Program, admitted at the end of the Presidential AIDS Advisory Panel debate, that there is a general lack of standardization of the definition of AIDS throughout the world [5]. After 15 years of research there is the lack of a ‘gold standard’ against which to measure the accuracy and reliability of the data generated from the commonly used methods to diagnose HIV infection; and the major task ahead was to develop such a golden standard.

Duesberg and colleagues show that different “risk groups” for AIDS disease have different conglomerates of “AIDS-defining” diseases. While Duesberg believes the AIDS disease does exist, Rasnick has argued consistently that AIDS does not exist and that it would “disappear instantaneously if all HIV testing was outlawed and the use of antiviral drugs terminated.”

For example, Kaposi’s sarcoma (a form of cancer) and Pneumocystis pneumonia are highly representative diseases among male homosexuals. But both of those are absent or rare among African AIDS cases. Similarly, tuberculosis is highly represented among Africans but absent or rare among male homosexuals. More tellingly, haemophiliacs who risk infection from blood transfusions have no highly representative diseases at all, only two common infections - yeast and Pneumocystis pneumonia - thereby distinguishing them from all other risk groups.

AIDS and recreational drugs

At least 35 published studies have linked illicit recreational use of drugs such as nitrite and other inhalants, amphetamines, cocaine, heroin, steroids, with AIDS, the most recent published in 2002.

Shortly after the AIDS epidemics in US and Europe began, researchers have indeed found that illicit psychoactive and aphrodisiac drugs consumed at massive doses were the common factors and probable causes of AIDS. Drugs such as cocaine, heroin, nitrite inhalants, amphetamines, steroids and lysergic acid had become widely available and popular in US and Europe in the “drug explosion” during and after the Vietnam war, which coincided with the era of “gay liberation”.

The drug explosion rose steeply from 1980 to a peak between 1990 and 1995, and thereafter declined due to government crackdown. The time course of the drug explosion correlates well with the number of AIDS cases, which rose from zero in 1980 to a sharp peak between 1992 and 1993 before declining sharply. Data from the CDC (Centers for Disease Control) for 1983 showed that all 120 male homosexual at risk for AIDS and 50 with AIDS were drug users. Consequently, many AIDS researchers favoured the hypothesis that drug-use or “lifestyle” was the cause of AIDS well into the 1990s [6].

“African ‘epidemic’ caused by poverty”

In contrast, the African epidemic is caused by poverty - malnutrition and lack of drinkable water [7,8] – which is consistent with its random distribution in the population. According to some researchers, it is the same traditional diseases of the poor reclassified as AIDS (see “African AIDS epidemic?” this series).

The problems begin with the diagnosis of AIDS, which, in Europe and the United States though not in Africa, is based on detecting anti-HIV antibodies that is poorly standardized and prone to false positives, and also poorly correlated with the presence of the virus or other ‘surrogate markers’ of AIDS disease, such as the level of CD4+ cells. According to Duesberg [5], African studies of patients diagnosed clinically as having AIDS showed that 50% were later found to be HIV-negative, that is, free of anti-HIV antibodies.

African AIDS also have a different conglomerate of “AIDS defining” diseases compared to other risk groups (see above).

“AIDS caused by anti-AIDS drugs”

Most if not all HIV positive individuals with no sign of AIDS disease would remain healthy, according to Duesberg, especially if they avoid anti-HIV drugs like AZT and newer cocktails.

Since 1987, thousands of US citizens and Europeans with AIDS, and since 1990, even larger numbers of healthy HIV-positive people have been placed on lifetime prescriptions of toxic drugs like azidothymidine (AZT), which terminates DNA synthesis, and protease inhibitors aimed at suppressing assembly of the virus. Since 1996, DNA chain-terminators were mixed with HIV protease inhibitors in drug cocktails.

By 2002, more than 450 000 US citizens were taking drug cocktails to prevent or cure AIDS, and well over half of the 450 000 were clinically healthy at the time they started the anti-HIV drugs. The healthy HIV-positives were treated according to the slogan, “Time to hit HIV, early and hard”, introduced by the New England Journal of Medicine in 1995 [9].

Duesberg and colleagues cited at least 63 scientific papers documenting diseases and death of HIV positive people placed on anti-HIV drugs over and above those in untreated controls. The diseases include AIDS-defining ones like immunodeficiency, leukopenia (low white blood cell count), fever, dementia, weight loss, lymphoma and diarrhoea; plus a host of others that are non-AIDS defining: anaemia, neutropenia (low neutrophil count), nausea, lipodystrophy (redistribution of body fat), muscle atrophy, mitochondrial dysfunction, hepatitis, birth defects, nephritis (inflammation of the kidney), lactic acidosis, heart infarct.

Similarly, at least 12 papers describe diseases and death in HIV negative human babies and in HIV negative animals treated with anti-HIV drugs before and after birth. The HIV negative babies were born to mothers who have all been treated with AZT, which was found to reduce the natural transmission of HIV by 50% to 70%.

When the HIV infected infants born to mother taking AZT during pregnancy, however, the results showed that the children born to AZT+ mothers were 1.8 times more likely to develop severe disease, 2.4 times more likely to have severe immune suppression, and 3.2 times more likely to die than those born to AZT- mothers [10].

There is little doubt that the drugs are associated with numerous side effects including those that are “AIDS defining”. Evidence of toxicities has been accumulating throughout the late 1990s. This finally led the US government to appoint a panel of AIDS researchers to review the situation. In 2001, it issued recommendations to restrict prescriptions of anti-HIV drugs, and that [11] “treatment for the AIDS virus be delayed as long as possible for people without symptoms because of increased concerns over toxic effects of the therapy.”

Why not test Duesberg’s chemical hypothesis?

Although there is extensive circumstantial evidence to support Duesberg’s chemical hypothesis, at least for some significant population of patients diagnosed with AIDS, it is difficult to prove without appropriate long-term controlled trials of anti-viral drugs.

If they are right, they claim, “AIDS would be entirely preventable by banning anti-HIV drugs, by publicizing that recreational drugs cause AIDS and by adequate nutrition. Moreover, many AIDS patients could still be saved from fatal damage by drug intoxication, if their AIDS-defining diseases were treated with time-proven, disease-specific medications.”

If they are wrong, then many AIDS sufferers who could benefit from anti-HIV therapy, will be misled. Though this problem can be addressed by much more closely monitored and selective anti-HIV drug administration.

Many researchers who think that HIV does cause AIDS, admit that progression to disease – defined by low CD4 cell count and high viral load (see Box 1) - can vary, and can be significantly affected by cofactors including injecting drug use and malnutrition. Others believe that HIV is necessary, though not sufficient, for causing AIDS disease. Vejko Veljkovic, AIDS virologist in Belgrade, Yugoslavia, says, “AIDS is syndrome and its different manifestations in different risk groups is not surprising because cofactors which plays an important role in the AIDS development are different.” Thus, toxic chemicals and drugs may be among the cofactors that trigger the AIDS disease. Many cofactors induce the production of cytokines, and can suppress the immune system independent of HIV.

So why do current AIDS researchers not investigate, and not even consider the role of chemicals in AIDS or study other non-HIV-AIDS theories to solve the AIDS dilemma?

Duesberg and colleagues blame “the structure of the large, government-sponsored research programs that dominate academic research since World War II”, which favour an establishment that can imposed sanctions on dissenters via the “peer review system”. The most powerful of the sanctions imposed are denial of funding and of publication.

Peer review is devolved to anonymous experts who do not fund applications that challenge their own interests. The review by Duesberg, Koehnlein and Rasnick [2] was blocked twice in the course of more than three years by the peer review process in two separate journals before it finally appeared in print.

Perhaps the biggest hurdle to resolving the controversy is the failure of both sides to acknowledge the full complexity of the immune response. I am entirely persuaded that recreational and toxic anti-HIV drugs as well as malnutrition can all undermine the immune system to produce immune deficiency syndromes. But I would certainly not like to exclude something like HIV that could target the immune cells directly, but that would be a whole new chapter by itself.

Article first published 30/3/2004

References

1. Duesberg PH. Retroviruses as carcinogens and pathogens: expectations and reality.Cancer Res 1987, 47, 1199-1220.
2. Duesberg P, Koehnlein C and Rasnick D. The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral therapy and malnutrition. J. Biosci 2003, 28, 383-412.
3. The Durban Declaration. Nature 2000, 406, 15-16.
4. Stewart GT, Mhlongo S, de Harven E, Fiala C, Koehnlein C, Herxheimer A, Duesberg P, Rasnick D. Giraldo R, Kothari M, bialy H and Geschekter C. The Durban Declaration is not accepted by all. Nature 2000, 407, 286.
5. Presidential AIDS Advisory Panel Report, a synthesis report of the deliberations by the panel of experts invited by the President of the Republic of South Africa, the Honourable Mr. Thabo Mbeki, March 2001.
6. Oppenheimer GM. Causes, cases and cohorts: The role of epidemiology in the historical construction of AIDS. In AIDS: The making of a chronic disease (E Fee and DM Fox, eds), pp 49-83, University of California Press, Berkeley, 1992.
7. Mims C and White DO. Viral Pathogenesis and Immunology, Blackwell, Oxford, 1984.
8. Seligmann M, Chess L, Fahey JL, et al. AIDS-an immunologic reevaluation. N Engl J Med 1984, 311, 1286-92.
9. Ho DD. Time to hit HIV, early and hard.N Engl J Med 1995, 333, 450-1.
10. 10. The Italian Register for HIV Infection in Children. Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AIDS 1999, 13, 927-33.
11. Altman L. US Panel seeks changes in treatment of AIDS virus. New York Times, 4 February 2001.