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Unravelling AIDS
What is the real extent of the AIDS epidemic? Why does AIDS attract so
much controversy? Do conventional anti HIV drugs do more harm than good? Are
there safe and effective treatments that can be made widely available at
affordable costs?
This special mini-series is part of an in-depth report, Unravelling
AIDS, to be published by ISIS later this year.
If you are interested in reserving a copy of the full report at a
special prepublication price of £7.50, please e-mail sam@i-sis.org.uk
ISIS Report 30/3/2004
AIDS & HIV?
Does HIV cause AIDS? Is AIDS a single disease? Do anti-viral drugs really
help? Dr. Mae-Wan Ho investigates
A fully referenced
version of this report is posted on ISIS
member's website. Full details here
Box 1
AIDS as commonly defined
AIDS (Acquired Immune Deficiency Syndrome) is the final and most serious
stage of Human Immunodeficiency Virus (HIV) disease. HIV causes AIDS.
The virus attacks the immune system and leaves the body vulnerable to
a variety of life-threatening illnesses and cancers.
HIV is transmitted through sexual contact, through blood (via blood
transfusions) or needle sharing (in injecting drugs use), and from mother
to child in pregnancy or during nursing.
The Centers for Disease Control has defined AIDS as beginning when
a person with HIV infection has a CD4 cell (a type of immune cell) count
below 200. It is also defined by numerous opportunistic infections and
cancers that occur in the presence of HIV infection.
The symptoms of AIDS are primarily the result of infections that do
not normally develop in individuals with healthy immune systems. These
are called “opportunistic infections.”
Common symptoms are fevers, sweats (particularly at night), swollen
glands, chills, weakness, and weight loss.
The AIDS-related infections and cancers that people with AIDS acquire
as their CD4 count decreases are as follows.
CD4 count below 350/ml: Herpes Simplex Virus causing ulcers
in the mouth or genitals; Tuberculosis;oral or vaginal thrush due to
yeast infection; Herpes zoster causing ulcers over a discrete patch
of skin; non-Hodgkins lymphoma or cancer of the lymph glands.
CD4 count below 200/ml: Pneumocystis carinii pneumonia; Candida
esophagitis (painful yeast infection of the esophagus)
CD4 count below 100/ml: Cryptococcal meningitis (infection
of the brain by this fungus); AIDS Dementia; Toxoplasmosis encephalitis
(infection of the brain by this parasite frequently found in cat feces);
progressive multifocal leukoencephalopathy (a viral disease of the brain
caused by the JC virus that results in a quick decline in cognitive
and motor functions); wasting syndrome (extreme weight loss and anorexia)
CD4 count below 50/ml: Mycobacterium Avium (a blood infection
by a bacterium related to tuberculosis; Cytomegalovirus infection (a
viral infection that can affect almost any organ system, especially
the eyes.
There is currently no cure for AIDS. However, several treatments are
available that can delay the progression of disease for many years and
improve the quality of life of those who have developed symptoms. Antiviral
therapy suppresses the replication of the HIV virus in the body. A combination
of several antiretroviral agents, termed Highly Active Anti-Retroviral
Therapy (HAART), has been highly effective in reducing the number of
HIV particles in the blood stream (as measured by a blood test called
the viral load). This can help the immune system bounce back for a while
and improve T-cell counts.
However, HIV tends to become resistant in patients who do not take
their medications every day. Also, certain strains of HIV mutate easily
and may become resistant to HAART especially quickly.
Treatment with HAART is not without complications. HAART is a collection
of different medications, each with its own side effect profile. Some
common side effects are nausea, headache, weakness, malaise, and fat
accumulation on your back and abdomen ("buffalo hump," lipodystrophy).
When used long-term, these medications may increase the risk of heart
attack by affecting fat metabolism.
Medications are also used to prevent opportunistic infections (such
as Pneumocystis carinii pneumonia) and can keep AIDS patients healthier
for longer periods of time. Source: Medical Encyclopedia, MedlinePlus,
updated 6/12/2002
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“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).
Box 2
A brief history of HIV-AIDS hypothesis
In 1981, a new epidemic began to strike male homosexuals and intravenous
drug users in the United States and Europe. The US Centers for Disease
Control (CDC) termed the epidemic, AIDS, for acquired immunodeficiency
syndrome.
Between 1981 and 1984, leading researchers, including those from CDC
proposed that recreational drug use was the cause of AIDS.
But in 1984, the US government researchers proposed that a virus, now
termed human immunodeficiency virus (HIV), is the cause of the epidemic
in US and Europe, and also in Africa.
This hypothesis - HIV causes AIDS – gained instant acceptance within
the scientific community.
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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 13th 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 Medicinein 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.
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