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In March 1988, the headline of a news article in Science called Peter Duesberg a “rebel
without a cause of AIDS.” But Duesberg says he’s a rebel with several causes of AIDS—it’s just that none of them happen to be the consensus favorite, HIV. Among the causes
he favors (at least for homosexuals and users of injectable drugs, the groups hardest hit by AIDS in the United States and Europe) are drugs. Specifically, he thinks the disease is
due to the use of illicit drugs such as heroin, cocaine, and amphetamines, as well as to the first drug approved for treating AIDS, AZT. “AIDS is new because the drug epidemic
is new,” argues Duesberg. “We’re in the middle of giving 200,000 people AZT for a hypothesis that’s at best unproven. … We’re telling 250 million Americans to use clean needles to inject cocaine and heroin. … What we should do is point out it’s not just against the law to use drugs, it may be against your health.”To make his case that drug use causes AIDS, Duesberg points out that drug use (in particular, use of nitrite inhalants known as “poppers”) has been high among some subgroups in the homosexual population. AIDS researchers agree. But beyond that, his contention that illicit drugs cause AIDS has provoked heated disagreement. Showing how heated the conflict between Duesberg and the majority of AIDS researchers has become, last year Duesberg charged that the authors of a study in Nature showing that only HIVpositive drug users developed AIDS had fabricated data; the charge was found to be groundless by an independent panel at the University of California, Berkeley.
Duesberg builds what he calls his “drug- AIDS” hypothesis using a variety of studies
he says show that “a critical lifetime dosage of drugs appears necessary in HIV-positives
and sufficient in HIV-negatives to induce AIDS-indicator and other diseases.” To
make the case that drugs are sufficient to cause AIDS in HIV-negatives, Duesberg
highlights data he argues show AIDS-like immune abnormalities and diseases in longterm drug users.
For example, Duesberg cites a study of drug users, both HIV-negative and HIVpositive,
in which a Dutch group examined the ability of the drug users’ T lymphocytes
to kick into action when stimulated. T lymphocytes are an important set of immunesystem cells that circulate in the blood; CD4 cells, the group whose progressive decline is the hallmark of AIDS, are a subset of T lymphocytes.
The Dutch group found that, among both HIV-positive and HIV-negative
drugs users, T cell reactivity decreased as the frequency of injection increased; Duesberg
cites this among his evidence that drug use can cause AIDS. But critics of Duesberg’s work say the study actually undermines his case. First, they say, he does not mention that among the drug users in the study who were HIVnegative, the chief indicator of the immune deficiency seen in AIDS—CD4 count—was well within the normal range. The 49 HIVnegative users who injected themselves more than 50 times a month had a mean of 990 CD4s (the normal range is from 600 to 1200); the 55 users who injected from one to 49 times a month had 910 CD4s. The HIVpositive drug users, on the other hand, had a
mean CD4 count of 450, less than half the CD4 count among the HIV-negative group
(Although typically not low enough to cause clinical symptoms). This study, say Duesberg’s critics, shows that the decline of CD4 cells—the hallmark of AIDS—is associated with HIV status and not with drug use. Duesberg counters that this study does not report lifetime dosages of drugs—only current frequency of injections. “Thus the frequent injectors may include more newcomers than the less frequent injectors,” he says.
In other words, the frequent injectors who were HIV-negative may actually have lower
lifetime dosages, and so their drug-caused immune deficiency has not shown up yet.
To test Duesberg’s hypothesis, one of the co-authors of the Dutch study, Roel Coutinho of Amsterdam’s Municipal Health Service, has compared HIV-positive and
HIV-negative drug users while controlling for the length of time the two groups injected
drugs. Coutinho compared 86 HIV-negative and 70 HIV-positive drug users who had REVIEWING THE DATA–IV Could Drugs, Rather Than a Virus, Be the Cause of AIDS? been injecting for a mean of 7.6 and 9.1 years, respectively. When the duration of
drug use was controlled, there was a clear difference between the two groups in CD4
status. Among those not infected with HIV, the base line CD4 count was 914,
within the normal range. Among those infected with HIV, however, the base line was
only 395, well outside the normal range. Between 1989 and 1994, CD4s remained stable
in the HIV-negative group but declined steadily among those infected with the virus.
And death from AIDS was associated with HIV status but not with drug use alone.
Among HIV-positives, there were 25 deaths, 10 attributable to AIDS; among HIV-negatives there were eight deaths, none due to AIDS-defining diseases. Other checks of the theory that drug use can cause AIDS raise just as many questions.
For example, there is evidence that heroin can cause immune abnormalities—but not
the type seen in AIDS. According to Rockefeller University’s Mary Jeanne Kreek, who studies immune responses in heroin addicts, heroin users do not experience a decline
in CD4 counts unless they are infected with HIV. Indeed, in 1989 Kreek reported in
the Journal of Pharmacology and Experimental Therapeutics that 11 long-term heroin user had a mean of 1500 CD4s—a significant elevation from the norm and the opposite of what is seen in AIDS. “Heroin is a blessedly untoxic drug,” concludes Kreek.
If Duesberg’s effort to show that AIDS can be caused by drug use alone elicits sharp criticism, his critics say that his attempt to find AIDS-defining illnesses among those
not infected with HIV is also problematic. One piece of research Duesberg cites to
show that HIV-negative drug users have AIDS-defining illnesses is a 1992 study from Johns Hopkins University. In his 1992 paper in Pharmacology and Therapeutics Duesberg says that in the Hopkins study, the fraction of the 160 HIV-negative people with AIDSdefining diseases was roughly equal to the fraction of the 590 HIV-positives with AIDS-related conditions. Duesberg refers to a table in the paper listing “clinical symptoms,” which are defined in a footnote as oral thrush (a mouth infection
caused by the fungus Candida albicans), fatigue, chronic diarrhea, weight loss, and
shortness of breath. But Hopkins epidemiologist Alvaro Muñoz, the study’s first author, says “None of these clinical symptoms were AIDS.” Muñoz says his statement is based on the definition of AIDS developed by the Centers for Disease Control and Prevention (CDC). That definition is specific about the type of weight loss that is considered AIDS-defining. A weight loss of greater than 10% combined with at least two loose stools per day for 30 days constitutes the AIDS-defining “HIV wasting syndrome.” The patients in the Hop- PETER C. HOWARD/JOHNS HOPKINS UNIV.
SCIENCE • VOL. 266 • 9 DECEMBER 1994 1649 CONCORDE RESULTS
kins study did not meet this definition. When Science asked Duesberg about Muñoz’s claim, Duesberg said: “These are HIV-free drug users. How do you think? they lost weight, even if it’s 9.8% or 10%? How do you think they got diarrhea?”
Nor did Duesberg accept CDC’s definition of another AIDS-defining illness:
esophageal candidiasis. This illness is caused by the same agent as oral thrush,
but it occurs in the esophageal passage, a distinction Duesberg characterizes as
arbitrary: “I know, 10 centimeters down the throat is candidiasis, and 11 centimeters
is AIDS.”
But clinicians who specialize in treating AIDS patients say the distinction is
not arbitrary. Science asked Joseph Sonnabend, a New York clinician specializing in
treating AIDS patients, whether the distinction is clinically well founded. Sonnabend,
an early Duesberg sympathizer who now says he thinks Duesberg has not
been open enough to evidence that HIV is involved in causing AIDS, says: “Oral thrush
occurs in people who are relatively immunologically intact. Esophageal candidiasis is
more or less confined to people who are much worse off, immunologically speaking.”
When the definitions established by CDC are used, the Hopkins study reveals that
none of the HIV-negative patients had AIDS-defining illnesses, while 47 of 590
HIV positives did.
In addition to heroin and cocaine, Duesberg argues that AZT, the very drug designed
to treat AIDS, can, in fact, cause it. And even his severest critics concede that AZT
is no wonder drug. Although it is one of the few drugs approved for fighting AIDS, AZT
can be severely toxic, and there is compelling evidence that the drug probably doesn’t help infected people live longer unless they already have full-blown AIDS.
Yet those reservations pale next to the position of Duesberg, who contends AZT is “AIDS by prescription.” Duesberg attacks AZT on several different levels. His most sweeping attack is on the rationale mfor using AZT in AIDS therapy. AZT
interrupts synthesis of viral DNA, and in so doing prevents HIV from replicating, which
AIDS researchers say is necessary for the virus to cause disease. But Duesberg notes
that AZT is not specifically targeted against the DNA of the virus but against DNA synthesis. “Since DNA is the central molecule of life, AZT treatment is not compatible
with life,” he wrote in response to questions from Science.
While mainstream AIDS researchers say Duesberg is correct in noting that AZT is
toxic because it interrupts DNA synthesis generally, that contention, they say, is a far
cry from claiming that the drug causes AIDS. And researchers who have conducted large-scale studies of the drug’s effects say that it does not cause the fatal illness.
The most comprehensive data on AZT come from the “Concorde”—the largest, longest running study of the drug. This 3-year, British-French study included 1749 HIV-positive people who initially showed no AIDS symptoms. Because of its largenumbers, Concorde has more statistical power than the seven other major AZT trialsto date combined. The main conclusion of the Concorde’s investigators was that patients treated with AZT soon after entering the study (the “Imm” group) fare no better than those who defer use or do not take the drug (the “Def ” group). The study did show, however, that the Imm group had fewer AIDS-related diseases during the first year of the study than the Def group did.
That wasn’t a very hopeful finding: AZT clearly isn’t a very effective anti-AIDS drug. But gloomy as those conclusions are, the Concorde’s principal investigators disagree sharply with Duesberg’s hypothesis that AZT, rather than HIV, causes AIDS. The Concorde data in “no way argue in favor of the hypothesis that AIDS is caused by AZT,”
Concorde’s French principal investigator, Maxime Seligmann of Paris’ Hopital Saint-Louis, wrote Science in response to a query. Duesberg, however, does not accept this
conclusion. In his written response to questions from Science, Duesberg wrote: “The Concorde data exactly prove my point: The mortality of the AZT-treated HIV-positives was 25% higher than that of the placebo group.” But the method he uses to arrive at thatfigure is sharply disputed by experts in clinical trials. Duesberg notes that there were 96 total deaths in the Imm group and only 76 in the Def group. He therefore concludes that the mortality rate among those given AZT immediately is 25% higher than among those who take it later. One problem with this analysis, say experts familiar with the Concorde data, is that it includes 22 deaths from events such as traffic accidents and suicides.
Subtracting deaths that were not related to AZT or AIDS yields 81 Imm deaths and
69 Def deaths. In addition, say the critics, there is a deeper flaw in Duesberg’s analysis: He does not take account of the total number of people in the Imm and Def groups. His reasoning for ignoring the denominator is, as he told Science in an interview, that “it was the same in the two groups.” But National Institute of Allergy and Infectious Diseases Director Anthony Fauci says this type of analysis means “ignoring an important part of a calculation.” Specifically, there were 96 total deaths out of 877 in the Imm group, implying that 10.9% of the people who were immediately treated with AZT died. In the deferred treatment group, there were 76 deaths among 872 people, or 8.7%. The appropriate conclusion, say the authors of the Concorde study, is that the difference
in mortality between Imm and Def groups is not 25% but 10.9% minus 8.7%—or 2.2%. Subtracting the deaths from causes unrelated to AZT or AIDS, the difference drops to 1.3%. As the Concorde paper notes, neither difference (2.2% or 1.3%) is statistically
significant. “If the Concorde study showed anything, it showed that AZT’s benefit is of limited duration,” says Fauci, referring to the fact that the Imm group had fewer AIDS-related illnesses during the study’s first year. Duesberg replies that “according to my analysis of this paper, this paper shows that AZT is harmful … 25% more people die in the AZT group than in the placebo group.
That matters to me. Because even a single life seems to matter to me. Maybe not to you. You like to normalize that. To me it does. Period.”–Jon Cohen §ARC is AIDS-related complex, a pre-AIDS condition.
* Includes six deaths (4 Imm, 2 Def) possibly HIV-related or drug-related and excludes 22 (15 Imm, 7 Def) unlikely to be HIV-related or drug-related.
** As first event.
*** A measure of statistical significance.
Characteristic HIV positive HIV negative
Total 70 86
Female 18 24
Mean age 31.9 31.4
Mean years regularly 9.1 7.6 injecting drugs
Recent injecting
Not injected 18 23
< daily 20 18
≥daily 32 45
Total deaths 25 8
AIDS 10 0
Overdose 4 3
Suicide 1 3
Pneumonia/sepsis 3 1
Other 7 1
AMSTERDAM DRUG STUDY SOURCE: R. COUTINHO, M. LANGENDAM, H. VAN HAASTRECHT, AMSTERDAM MUNICIPAL HEALTH SERVICE.
“Imm” group “Def” group (n = 877) (n = 872) Log rank p***
Total deaths 96 76 0.13
HIV-related deaths* 81 69 0.34
AIDS or death** 176 171 0.94
ARC§, AIDS, or death** 267 284 0.18
Advanced ARC, AIDS,
or death 191 186 0.91
SOURCE: CONCORDE COORDINATING COMMITTEE/LANCET
Despite the fact that South Africa is home to more people living with HIV that any other country in the world its President Thabo Mbeki denies knowing anyone affected by the disease.
victims, told BBC News Online. Mbeki's stance on Aids has long been controversial. On Friday Mr Mbeki's spokesperson Bheki Khumalo reportedly confirmed that the president had made the controversial remark in an interview with the Washington Post in New York this week. "Personally, I don't know anybody who has died of Aids," Mr Mbeki said, adding when asked whether he knew anyone with HIV, "I really, honestly don't". The statement has been sharply criticised by opposition politicians and Aids activists alike who say Mr Mbeki is "living in his own world". If it is true that the president said he knows no-one who has died of Aids then he needs to come and meet some real South Africans Xolani Kunene of Treatment Action Campaign "As usual it looks like Mr Mbeki is not living in the real South Africa... As president Mr Mbeki is the first citizen of South Africa, so he should be aware of this crisis," Xolani Kunene of Treatment Action Campaign (TAC), a South African organisation lobbying the government for affordable treatment for HIV and Aids
"We estimate that 600 South Africans are dying of Aids-related illness every day."
"If it is true that the president said he knows no-one who has died of Aids then he needs to come and meet some real South Africans, read the newspapers, visit sufferers and campaign groups like our own - we can assist him to see the problem," he added. Rumour mill Mr Mbeki's stance on Aids has been the subject of contention before - he has long maintained that there is no link between Aids and HIV, and this latest remark has raised eyebrows once more.
There were unconfirmed rumours the virus killed Mbeki's spokesman. Many think it inconceivable that with one in 10 South Africans infected with HIV the president could not personally know any sufferers. In the past there have been rumours that members of his staff and associates died as a result of the virus. Phakamile "Parks" Mankahlana, the presidential spokesman for both Nelson Mandela and Mr Mbeki, died in 2000 from what the presidential office described as a "long illness".
His premature death at the age of 36 led to intense speculation that the illness was Aids-related - although neither his family nor the authorities would say. Drugs controversy
"There were rumours, but these cannot be confirmed," said Mr Kunene.
Facts and figures on the impact of HIV in sub-Saharan Africa
At-a-glance
"The same was true of ANC member Peter Mokaba - there were lots of rumours that he died of Aids, but the authorities denied this saying that he had simply been ill for a long time and then died," he added. Mokaba, a fiery leader of the South African freedom struggle best known for his notorious anti-apartheid slogan "kill the Boer, kill the farmer" died in June 2002 from a respiratory illness which had first appeared three years earlier.
Many South Africans believed he suffered from Aids - a claim Mokaba vehemently denied.
As a politician Mokaba denied the existence of Aids and claimed that Aids anti-retroviral drugs were in fact "poison" that had no medicinal benefit. Sufferer's shame
HIV/Aids still carries a stigma in South Africa where public ignorance about the estimated five million infected people remains.
One in 10 South Africans are HIV positive TAC says that the shame associated with having the disease is slowly ebbing away, but that the country still needs high profile figures in government and the media who are suffering from the disease to come out and admit it. "But this doesn't really happen - of course there is a privacy issue, but also people think 'why should I bother?' as there is no benefit to revealing that you have the disease." "Saying you have HIV does not give you access to free drugs and treatment - it is not like saying you have diabetes, then you get packed off to the hospital for immediate free beneficial treatment," Mr Kunene added.
Diversion tactic
Opposition politicians have been quick to leap on Mr Mbeki's reported comments, with a statement from the Independent Democrats branding him a "dissident".
"Thabo Mbeki's interview with the Washington Post (if it is proven to be correct) has embarrassed the nation of South Africa," the statement said.
"Mbeki's statement proves that he is a dissident who believes that the HIV virus doesn't cause Aids... In the face of the economic evidence that South Africa is subjected to as a result of the HIV virus, it is a shame to think that the country is run by a dissident."
However, TAC say that some of Mr Mbeki's seeming lack of awareness about the plight of Aids sufferers may be a smokescreen. "He may be trying to divert attention from what the government really needs to do to tackle this crisis. The deadline for the health minister to come up with a plan to deal with the disease is the end of the month and it looks like the plan will be delayed," Mr Kunene said. "If Mr Mbeki comes out with a statement like this then it diverts the whole machine and instead we all run around addressing these latest comments."
Introduction to the AIDS controversy
A growing group of bio-medical scientists claim the cause of AIDS is stillunknown. These heretics do not believe in the lethal AIDS virus called HIV. They claim that the virus is indeed harmless. Most of them think AIDS is also not sexually transmitted; it probably has toxic causes. People die because they are poisoned to death by toxic antiviral drugs. Part of the AIDS dissidents even question the existence of a virus entity. These HIV skeptics say that the AIDS virus has never really been isolated, and the AIDS tests are worthless...
In April 1984, U.S. Health and Human Services Secretary Margaret Heckler announced to the world at a press conference that an American government scientist had discovered the probable cause of AIDS. This claim, made in the absence of the usual scrutiny and debate that is provided by refereed publication, was nonetheless received as fact by the general scientific community, and without further investigation a vast research program was launched. Based on the proposition that the newly identified retrovirus, termed HIV, is responsible for the apparently irreversible destruction of T-helper cells characteristic of AIDS patients, this program has until now been unsuccessful at providing either a vaccine or a cure, and has resulted in public health policies that are of questionable value in preventing the spread of AIDS.
Since 1987, data contradicting a single-virus etiology of AIDS have been accumulating. As a result, a loosely affiliated worldwide network ofscientists - The Group for the Scientific Reappraisal of the HIV-AIDS Hypothesis - was formed in an attempt to bring about an impartial investigation of the question that was inadequately considered in 1984:
Is HIV really the cause of AIDS?
As an explanation for the origin of AIDS, the HIV hypothesis is implausible because it contradicts a number of established principles of virology and immunology. It is also at variance with a growing body of empirical observations.
Some Examples:
Retroviruses do not typically kill their host cells. On the contrary, they depend on continued replication of the host for their own survival.
Viruses typically cause disease shortly after infection, before the immune system of their host can respond. There is no other example of a viral pathogen which causes primary disease only after long and unpredictable latent periods, only in the presence of neutralizing antibodies, and in the virtual absence of gene expression, as HIV is said to do.
The number of HIV carriers in the U.S. has remained constant at one million since 1985, when widespread antibody testing was introduced, yet new viruses spread exponentially in a susceptible population.
AIDS has remained confined to the same risk groups since it was first identified as a new disease syndrome, and there are many fewer cases than predicted.
Approximately 75% of American hemophiliacs have been infected with HIV for more than 10 years. According to the HIV hypothesis at least 50% should have died of AIDS by now, yet mortality among hemophiliacs has not increased and only 2% of HIV-positive hemophiliacs develop AIDS indicator-diseases annually.
The same diseases are found in similar frequencies in HIV positive and HIV negative intravenous drug users, and the overall mortality in the two groups is the same.
The HIV antibody tests are not standardized. No gold standard has been used and may not even exist to determine specificity. The tests are also not reproducible. The proteins which are considered to be specific to HIV may in fact represent normal cellular proteins. A positive test may represent nothing more than cross-reactivity with the many non-HIV antibodies present in AIDS patients and those at risk.
Despite these and many other inconsistencies, the HIV-AIDS hypothesis remains the sole basis for the public health policies that are aimed at controlling the spread of AIDS by advocating (1) "safe-sex" practices, (2) the use of "clean" needles to inject toxic, unsterile drugs, and (3) the long-term administration of potent metabolic poisons, like AZT, which are claimed to prolong the lives of HIV-infected persons; and for research programs directed almost exclusively at developing pharmaceuticals designed to interfere with HIV replication.
If HIV does not cause AIDS, what does?
Duesberg is certain that the primary cause of AIDS among American homosexual men is drug abuse. The drugs in question suppress the immune system's ability to combat infections, and at least some of these chemicals are carcinogens as well. That is, they cause cancer. Examples of cancer-causing and supposedly AIDS-causing drugs include the "poppers" widely used by homosexuals in the "bath houses" of San Francisco. One particular cancer has long been used to diagnose AIDS among these men. It affects the blood vessels of the face and lungs, and is called "Kaposi's sarcoma." Though most AIDS researchers believe the virus itself causes Kaposi's sarcoma, Duesberg believes the poppers cause it, and he points to the fact that the nitrites are inhaled -- the cancer usually appears on the face and/or in the lungs of the afflicted. He also points to the absence of virus from the sarcoma tissue. If this isn't a startling enough challenge to the conventional view, Duesberg further maintains that AZT, one of the chemicals used to treat AIDS patients, causes AIDS instead. If true, this would indeed be a cruel and ironic twist of fate for those HIV-positive patients undergoing treatment. A second risk group is said to be the population of hemophiliacs. Before blood supplies were screened to keep out HIV, the virus was transmitted by transfusion. Of course, the traditional view of HIV as a cause of AIDS allows hemophiliacs to become infected by other means too. Chief among these risks for people in general is unprotected sex by which the virus is transmitted through seminal or vaginal fluids. Duesberg believes the immune system of hemophiliacs is suppressed by the accumulated effect of foreign proteins received with every transfusion.
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