|
The Role
of Drugs in the Origin of AIDS
Biomed
& Pharmacother
Vol.46, pp.
3-15, 1992
Dossier
Peter H. Duesberg
Department
of Molecular and Cell Biology
229 Stanley Hall
University of California Berkeley
Berkeley, CA 94720, USA
(Received 28 November 1991; accepted 10 December 1991)
Summary
-- It is proposed that the new American and European AIDS epidemics
are caused by recreational and anti-HIV drugs rather than by human
immunodeficiency virus (HIV). Chronologically, the AIDS epidemic
in the 1980s followed a massive escalation in the consumption of
recreational drugs that started in the 1960s and 70s. Epidemiologically,
both epidemics derive about 80 % of their victims from the same
groups of 20-44 year-olds, of which 90 % are males. In America 32%
of these are intravenous drug users and an unknown percentage are
prescribed the cytotoxic DNA chain terminator AZT, as inhibitor
of HIV. Direct evidence indicates that these drugs are necessary
for HIV-positives and sufficient for HIV-negatives to develop AIDS
diseases. The drug-AIDS hypothesis predicts correctly that: (i)
AIDS is new in the US, because the drug epidemic is new, while the
HIV epidemic is old -- fixed at a constant 1 million Americans since
1985; (ii) despite an increase in venereal diseases, AIDS remains
restricted to long-term drug users and small groups with clinical
deficiencies; (iii) over 72 % of AIDS occurs in 20-44 year old males,
because they make up over 80% of hard psychoactive drug use; (iv)
distinct AIDS diseases correlate with the use of distinct drugs,
eg Kaposi's sarcoma with nitrite inhalants, tuberculosis with intravenous
drugs, and leukopenia, anemia, and nausea with AZT; (v) AIDS diseases
are only acquired after long-term drug consumption, rather than
after single contacts as the virus-hypothesis predicts. The drug
hypothesis can be tested epidemiologically and experimentally in
animals. It predicts that most AIDS can be prevented by stopping
the consumption of drugs, and provides a rational basis for therapy.
Was
ist das Schwerste von allem?
Was
Dir das Leichteste duenkt:
mit
den Augen zu'sehen
was
vor den Augen Dir liegt.
What
is the most difficult of all?
That
which seems easiest to you:
to
see with your eyes,
what
is in front of your eyes.
(Xenien,
Goethe)
Introduction
AIDS is a new
syndrome of 25 previously known diseases (19,62,63), In American
63% are microbial diseases such as pneumonia, candidiasis, tuberculosis,
cytomegalovirus, and herpes virus disease (18,19) that result from
immunodeficiency due to a severe depletion of T-cells (62, 63).
The remaining 37% of AIDS diseases are dementia, wasting disease,
Kaposi's sarcoma, and lymphoma which are not caused by, and not
consistently associated with immunodeficiency and microbes (18,
33, 36, 115) In the US 32% of AIDS patients are intravenous drug
users (18, 86), about 60% are male homosexuals [18], and most of
the remainder have sever clinical or congenital deficiencies, including
hemophilia [18,33 100]. Over 80% of the American AIDS patients are
20-44 year olds, of which about 90% are males [18]. Different AIDS
risk groups have different AIDS diseases. For example, homosexuals
have 20 times more Kaposi's sarcoma than other AIDS patients [7],
intravenous drug users have a proclivity for tuberculosis [12,114],
crack (cocaine) smokers exhibit pneumonia [41], and users of the
cytotoxic DNA chain terminator AZT, prescribed to inhibit human
immunodeficiency virus (HIV) develop anemia, leukopenia and nausea
[94, 99, 113].
Currently most
medical scientists believe that AIDS is caused by HIV [62, 63].
This hypothesis assumes: 1) that HIV is new and therefore AIDS is
new in all countries with HIV [9]; 2) that AIDS is acquired by sexual
and parenteral transmission of HIV [62, 63]; and 3) that AIDS occurs
in the presence of antibodies to HIV (a positive AIDS virus [6,
33, 48].
However, each
of these assumptions has been invalidated:
1) HIV has
long been established in the US, fixed to an extremely constant
reservoir of about 1 million carriers, ever since 1985 when it became
possible to detect antibody against it with the AIDS test [33, 122].
This indicates that the HIV epidemic is old in America, because
new microbes spread exponentially in a susceptible population [46].
Thus HIV is not a plausible cause for a new epidemic.
2) HIV is naturally
transmitted from mother to child at an efficiency of about 50% [33].
The real efficiency may be higher than serological tests indicate
because some latent proviruses only become activated with advanced
age [33, 95]. By contrast, sexual transmission of HIV is highly
inefficient, depending on an average of about 1,000 sexual contacts
[33, 71] because there is no HIV in semen from 1 out 25 anti-body-positive
men [121]. It follows that HIV depends on perinatal transmission
for its survival [33]. Since retroviruses [37] and other viruses
[42, 80] that survive from perinatal transmission cannot be fatally
pathogenic, HIV is probably harmless.
3) Within weeks
after horizontal infection HIV activity is "rapidly and effecti
to less than 1 in 10,000 T-cells [36]. This immunity does not protect
against AIDS, eliminating a role for HIV in AIDS.
Indeed there
are numerous inconsistencies between AIDS and infectious disease:
1) There is
not even one confirmed case of a health care worker who contracted
AIDS from a patient, although there were over 160,000 AIDS patients
in the US in the last 10 years [18,36] and there is no antiviral
vaccine or drug. Likewise not a single scientist has contracted
AIDS from the AIDS virus or from other microbes from AIDS patients,
which are propagated in hundreds of research laboratories and companies
[33, 36].
2) All new
infectious diseases spread exponentially in susceptible populations
[46]. However, despite widespread alarm, AIDS has since 1987 claimed
only about 30,000 or 0.03% per year from a reservoir of over 100
million susceptible, sexually active Americans, although conventional
venereal diseases are increasing in the US [5] and there is no anti-HIV
vaccine and no anti-HIV drug.
3) The distribution
of all infectious venereal diseases is almost even between the sexes
[65]. By contrast 90% of American AIDS is restricted to males since
1981 [18].
4) Almost all
(94%) of the Americans who develop AIDS have been subject to abnormal
health risks [18]. These risks include either long-term consumption
of recreational, psychoactive, and aphrodisiac drugs and anti-HIV
drugs like the cyctocidal DNA chain terminator AZT (see below) or
congenital or acquired deficiencies like hemophilia [18, 33]. This
indicates that specific health risks are necessary for AIDS.
5) The observations
that distinct AIDS risk groups have distinct AIDS diseases, eg homosexuals
having 20 times more Kaposi's sarcoma than HIV carriers from other
risk groups [7], intravenous drug users having a proclivity for
tuberculosis [12, 114], crack (cocaine) smokers for pneumonia [41],
and AZT users for leukopenia, anemia, lymphoma and nausea [50, 94,
99, 113, 130] are also hard to reconcile with a common infectious
cause.
6) All AIDS
diseases occur in all AIDS-risk groups in the absence of HIV [33].
Ironically, the monthly HIV/AIDS Survellance reports of the Centers
for Disease Control (CDC) never survey HIV in AIDS patients [18].
In view of
these inconsistencies between AIDS and infectious disease and the
total lack of a common, active microbe in AIDS, several investigators
have concluded that AIDS may not be infectious [3, 17, 33, 34, 56,
59, 61, 70, 77, 92, 96, 100]. Here the hypothesis is investigated
that American and European AIDS diseases, above their normal background,
are the result of the long-term consumption of recreational and
anti-HIV drugs.
Chronological
coincidences between the AIDS and the drug epidemics
The appearance
of AIDS in America in 1981 [62, 63], coincided with a massive escalation
in the consumption of psychoactive drugs [16, 44, 57, 73, 87, 89,
111]. The Bureau of Justice Statistics reports that the number of
drug arrests in the US has increased from about 450,000 in 1980
to 1.4 million in 1989 [16, 111]. About 500 kg of cocaine were confiscated
by the Drug Enforcement Administration in 1980, about 9,000 kg in
1983, 80,000 kg in 1989, and 100,000 in 1990 [16, 44, 131]. The
agency estimates that at most 20% of the cocaine smuggled into the
US is confiscated [4]. Cocaine-related hospital emergencies increased
5-fold from 1984 to 1988 [89]. The number of dosage units of domestic
stimulants, such as amphetamines, confiscated increased from 2 million
in 1981 to 97 million in 1989 [44].
Further, the
recreational use of psychoactive and aphrodisiac nitrite inhalants
began in the 1960s and reached epidemic proportions in the mid-1970s,
a few years before AIDS appeared [88]. The National Institute on
Drug Abuse reports that in 1979-80 over 5 million people used nitrite
inhalants in the US at least once a week [88], a total of 250 million
doses per year [128]. In 1976 the sales of nitrite inhalants in
one American city alone amounted to $50 million annually [88], at
$5 per 12-ml dose [106].
Since 1987
the cytocidal DNA chain terminator AZT is prescribed as an anti-HIV
durg [67, 130]. Currently about 80,000 HIV antibody-positive Americans
and 120,000 world-wide, with and without AIDS, take this drug [33].
Epidemiological
overlaps among drug-and AIDS-related health statistics
Drugs and AIDS
appear to claim their victims from the same risk groups. For instance
the CDC reports that the annual mortality of 25-44-year-old American
males increased from 0.21% in 1983 to 0.23% in 1987, corresponding
to about 10,000 deaths among about 50 million in this group [15].
Since the annual AIDS deaths had also reached 10,000 by 1987, HIV
was assumed to be the cause [18, 19, 62]. However, mortality in
25-44-year-old males from septicemia, considered an indicator of
intravenous drug use, rose almost four- fold from 0.46 per 100,000
in 1980 to 1.65 in 1987 and direct mortailty from drug use doubled
[15, 85], suggesting that drugs played a significant role in the
increased mortality of this group [15]. Moreover, deaths from AIDS
diseases and non-AIDS pneumonia and septicemia per 1,000 intravenous
drug users in New York increased at exactly the same rates, from
3.6 in 1984 to 14.7 and 13.6 respecitvely in 1987 [110]. In view
of this, the CDC acknowledges: "We cannot discern, however,
to what extent the upward trend in death rates for drug abuse reflects
trends in illicit drug use independent of the HIV epidemic"
[15]. Further, maternal drug consumption was blamed by some [119]
and HIV infection by others [18, 63] for a new epidemic of physiological
and neurological deficiencies, including mental retardation, in
American children.
Another striking
coincidence is that over 72% of all American AIDS patients [18]
and over 80% of all Americans who consume hard psychoactive drugs
[51, 87] or get arrested for possession of drugs [16] are 20-44-year-old
males. Thus there is substantial epidemiological overlap between
the two epidemics [73] reported as "The twin epidemics of substance
use and HIV" by the National Aids Commission [86].
Drug use
in AIDS risk groups
Intravenous
drug users generate a third of all AIDS patients
Currently 32%
of the American AIDS patients come from groups that use intravenous
drugs such as heroin, cocaine, and others [18, 86]. This group includes
about 75% of the heterosexual AIDS cases, 71% of the females with
AIDS, and over 10% of the male homosexuals and hemophiliacs with
AIDS [18, 86]. In addition, about 50% of American children with
AIDS were born to mothers who are confirmed intravenous drug users
and another 20% to mothers who had sex with intravenous drug users
and are thus likely users themselves [18, 86]. Likewise, over 30%
of European AIDS patients are intravenous drug users [26].
Homosexuals
who use oral drugs generate about 60% of American AIDS patients.
Approximately
60% of the American AIDS patients are 20-44-year-old male homosexuals
[18]. The following evidence indicates that they come from groups
who use oral psychoactive and aphrodisiac drugs. A survey of 3,916
self-identified American homosexual men, the largest of its kind,
reports in 1990 that 83% had used one, and about 60% two or more
drugs with sex during the previous 6 months [91]. These drugs include
nitrite- and ethyichloride inhalants, cocaine, amphetamines, methaqualone,
lysergic acid, phenylcyclidine, and more [2, 10, 27, 56, 70, 91,
96, 97, 100, 101, 112, 120, 126]. A study of a group of 359 homosexual
men from San Francisco reported in 1987 that 84% had used cocaine,
82% alkylnitrites, 64% amphetamines, 51% quaaludes, 41% barbiturates,
20% injected drugs and 13% shared needles [27]. About 74% had past
or current infection by gonorrhea, 73% by hepatitis B virus, 67%
by HIV, 30% by amoebae and 20% by syphilis [27]. This group had
been randomly selected from a list of homosexuals who had volunteered
to be investigated for hepatitis B virus infection and to donate
antisera to hepatitis B virus between 1978 and 1980. It is the same
group for which the 50% progression rate from HIV to AIDS was calculated
to be about 10 years [72, 83] and reported to be "relevant
for the population as a whole" [83].
Nitrite inhalants
and possibly other drugs are preferred by male homosexuals as aphrodisiacs
because they facilitate anal intercourse [81, 88, 91, 101]. For
example, an early CDC study that included 420 homosexual men found
nitrite use far more frequent among homosexuals than among heterosexuals
and correlated directlly with the number of different homosexual
partners [17]. Surveys studying the use of nitrite inhalants in
San Francisco found that among homosexual men 58% were users in
1984 and 27% in 1991 compared to less than 1% among hetrosexuals
and lesbians of the same age group [102].
An unknown
percentage of AIDS patients comes from groups of AZT users.
About 80,000
Americans and 120,000 persons world-wide, with and without AIDS,
currently take the cytocidal DNA chain terminator AZT [33] and an
unknown number take other DNA chain terminators like ddI and ddC
[113]. AZT has been prescribed since 1987 to symptomatic [43, 63,
67, 99], and since 1990 to asymptomatic carriers of HIV including
babies and hemophiliacs [38, 123], in an effort to inhibit HIV DNA
synthesis [130]. Thus an unknown, but possibly a high percentage
of the 30,000 Americans that currently develop AIDS per year [18]
have used AZT prior to or after the onset of AIDS. For instance,
249 out of 462 HIV-Positive, AIDS-free homosexual men from Los Angeles,
included in the above survey [91], are on AZT or ddI [84].
Drug use
necessary in HIV-positives and sufficient in HIV-negatives for AIDS
diseases
To distinguish
between HIV and drugs as causes of AIDS, it is necessary to identify
either HIV carriers that develop AIDS only when they use drugs or
to identify HIV-free drug users that develop AIDS indicator diseases.
Drug use
necessary for AIDS in presumed or confirmed carriers of HIV
1) Epidemiological
correlations indicate that nitrites are necessary for Kaposi's sarcoma:
a) a 27- to 58 fold higher consumption of nitrites [101, 102] correlates
with a 20-fold higher incidence of Kaposi's sarcoma in male homosexuals
compared to all other AIDS patients of the same age group [7]; b)
among male homosexuals, those with Kaposi's sarcoma have used nitrite
inhalants twice as often as those with other AIDS diseases [56];
c) during the last 6 to 8 years the use of nitrite inhalants among
male homosexuals decreased, eg from 58% in 1984 to 27% in 1991 in
San Francisco [102]. In parallel, the incidence of Kaposi's sarcoma
among American AIDS patients decreased from a high of 35% in 1983
[20] to a low of 10% in 1990 [18]. In fact, nitrites may be sufficient
causes for these diseases, because there was no evidence of HIV
infection in any of these studies.
2) Specific
correlations also indicate that nitrites are necessary for AIDS.
The first five cases diagnosed as AIDS in 1981, before HIV was known,
were male homosexuals who had all consumed nitrite inhalants and
presented with pneumocystis pneumonia and cytomegalovirus infection
[53]. Early CDC data indicate that in 1981 and 1982. 75% of male
homosexuals with AIDS had used oral drugs at least once a week and
97% occasionally [17, 57], and that every one of 20 Kaposi's sarcoma
patients had used nitrites [77]. The National Institute on Drug
Abuse reports correlations from 69% [68] to virually 100% [56, 88]
between nitrite inhalants and Kaposi's sarcoma and pneumonia. Again
drugs may have been sufficient to cause these diseases, because
HIV was not diagnosed.
3) The incidence
of AIDS diseases among 297 HIV-positive, asymptomatic intravenous
drug users over 16 months was three times higher in those who persisted
than in those who stopped injecting drugs [124].
4) The T-cell
count of 65 HIV-infected drug users from New York dropped over 9
months in proportion with drug injection, on average 35%, compared
to controls who had stopped [28].
5) A placebo
controlled study investigating AZT as AIDS prophylaxis in HIV-positive,
AIDS-free 25-45-year-old male homosexuals and intravenous drug users
indicates that AZT induces various diseases, including some in the
AIDS definition [123]. During one year of taking 500 mg AZT per
day aroup of 453 developed 11 AIDS cases, and a group of 457 taking
1500 mg AZT per day developed 14 cases. The placebo group of 428
developed 33 cases.
However, the
price for the presumed savings of 22 and 19 AIDS cases with AZT
was high, because 19 more cases of anemia, neutropenia and severe
nausea appeared in the 500 mg AZT-group and 72 more such cases appeared
in the 1500 mg AZT-group than in the placebo group. This indicates
cytocidal effects of AZT on hemopoiesis and on the intestines. Although
these AZT-specific diseases were not diagnosed as AIDS, neutropenia
generates immunodeficiency and thus AIDS. A loss of T-cells was
not reported in this study. This is surprising in view of previous
reports describing T-cell- and general bone marrow-toxicity of AZT
[32, 99, 130]. Moreover, 10 of the placebo group-specific AIDS diseases
were cancers and dementia, of which only 3 and 2 were observed in
the 500- and 1500 mg-AZT groups, respectively. This suggests a selection
bias in favor of more healthy subjects for the AZT groups. The study
is further compromised by the failure to report and to consider
the recreational drug use histories and the many compensatory treatments
of the subjects analyzed.
6) Within 48
weeks on AZT, 172 (56%) out of 308 Australian AIDS patients developed
one or more new AIDS diseases, including pneumonia and candidiasis
[116]. This indicates that AZT induces AIDS diseases with less than
1 year and thus much faster than the 10 years HIV is said to need
to cause AIDS [72]. Likewise, no therapeutic benefits were observed
in a study of 365 AIDS patients from France after six months on
AZT, but new AIDS diseases and approximately 50% leukopenias and
20% deaths occurred within nine months on AZT, Further, no therapeutic
benefits were observed in four Norwegian AIDS patients after six
months on AZT [98].
7) The annual
lymphoma incidence of AZT-treated AIDS patients was reported to
be 9% by the National Cancer Institute and was calculated to be
50% over 3 years [94]. The lymphoma incidence of untreated HIV-positive
AIDS risk groups is 0.3% per year and 0.9% per 3 years, derived
from the putative average progression rate of 10 years from HIV
to AIDS [33, 72, 83] and the 3% incidence of lymphoma in AIDS patients
[18]. Thus the lymphoma incidence is 30 to 50 times higher in AZT-treated
than in untreated HIV-positive counterparts. In addition, "during
the past three years [of AZT therapy] a progressive increase in
the number of [AIDS] patients dying from lymphoma...", to a
current total of 16%, was noted in 1991 in a group of 346 AIDS patients
in London, most of whom were on AZT [93].
It is likely
that the chronic levels of the mutagenic AZT (see below), at 10-33
pM (500-1500 mg/person per day), were responsible for the lymphomas.
The alternative proposal that HIV-induced immunodeficiency was responsible
for the lymphomas [94] is unlikely, since cancers do not reflect
a defective immune system [36, 115].
8) Ten out
of 11 HIV-positive AZT-treated AIDS patients recovered cellular
immunity after discontinuing AZT in favor or an experimental HIV
vaccine [107], suggesting that AZT was a sufficient cause of immunodeficiency.
9) Four out
of 5 AZT-treated patients recovered from myopathy 2 weeks after
discontinuing AZT; two redeveloped myopathy on renewed AZT treatment
[118], indicating that AZT was sufficient for myopathy.
10) Four patients
with pneumonia developed severe pancytopenia and bone marrow aplasia
12 weeks after the initiation of AZT therapy. Three out of 4 recovered
within 4-5 weeks after AZT was discontinued [50], indicating that
AZT was sufficient for pancytopenia.
Drug use
sufficient for AIDS indicator diseases in the absence of HIV
1) Among intravenous
drug users in New York representing a spectrum of HIV-related diseases,
HIV was only observed in 22 out of 50 pneumonia deaths, 7 out of
22 endocarditis deaths, and 11 out of 16 tuberculosis deaths [114].
2) Pneumonia
was diagnosed in 6 out of 289 HIV-free and in 14 out of 144 HIV-positive
intravenous drug users from New York [109].
3) Among 54
prisoners with tuberculosis in New York State 47 were street-drug
users but only 24 were infected with HIV [12].
4) In a group
of 21 heroin addicts, the ratio of helper to suppressor T-cells
declined within 13 years from a normal of 2 to less than 1, which
is typical of AIDS [19, 63], but only 2 were infected by HIV [31].
5) Thrombocytopenia
and immunodeficiency were diagnosed in 15 intravenous drug users
on average 10 years after they became addicted, but 2 were not infected
with HIV [104].
6) Lymphocyte
reactivity and abundance was depressed by long-term injection of
drugs not only in 111 HIV-positive but also in 210 HIV-free intravenous
drug users from Holland [79].
7) The same
lymphadenopathy, weight loss, fever, night sweats, diarrhea, and
mouth infections were observed in 49 out of 82 HIV- free, and in
about 40% of 113 intravenous drug users from France, of which 69
were HIV-positive and 44 were negative [40]. The French group had
used drugs for an average of 5 years.
8) Among 6
HIV-free male homosexuals with Kaposi's sarcoma, 5 have reported
the use of nitrite inhalants [47].
9) Similar
neurological deficiencies were observed among 12 HIV- infected and
16 uninfected infants of drug-addicted mothers [66].
Thus, the long
term use of recreational and anti-HIV drugs appears necessary in
HIV-positives and sufficient in HIV-negatives to induce AIDS indicator
and other diseases.
Toxic effects
of drugs used by AIDS patients
Toxicity
of recreational drugs
From as early
as 1990 [1] evidence has accumulated that addiction to psychoactive
drugs leads to immune suppression and clinical abnormalities similar
to AIDS, including lymphopenia, lymphadenopathy, fever, weight loss,
septicemia, and increased susceptibility to infections and neurological
disorders [13, 14, 30, 49, 55, 75, 78, 103, 110, 117, 120]. Intravenous
drugs can be toxic directly, or indirectly via malnutrition, both
because of their enormous expense and via septicemia, since most
illcit drugs are not sterile [15, 24, 73, 114]. Oral comsumption
of cocaine and other psychoactive drugs has been reported to cause
pneumonitis, bronchitis, edema, and other diseases [41]. In children
born to mothers addicted to cocaine and other drugs, physiological
and neurological deficiencies including mental retardation are observed
[100, 119]. According to the National Institute on Drug Abuse "Cocaine
is, from a public health perspective...the drug of the greatest
national health concern" [54]
Alkylnitrites
are directly toxic as they are rapidly hydrolyzed in vivo to yield
nitrite ions, which react with all biological macromolecules [70,
90]. Addicts with 0.5 mM nitrite derivatives and 70% methemoglobin
in the blood have been recorded [90]. Toxicity for the immune system,
the central nervous system, the haematologic system, and pulmonary
organs has been observed after short exposure to nitrites in humans
and in animals [88, 128]. Further, alkylnitrites were shown to be
both mutagenic and carcinogenic in animals [60, 64, 82]. Several
investigators have proposed that nitrite inhalants cause pulmonary
[33] and skin Kaposi's sarcoma and possibly pneumonia by direct
toxicity on the skin and oral mucosa [17, 59, 77]. In view of this,
a causal link between nitrite inhalants and Kaposi's sarcoma and
pneumonia in homosexuals was first suggested in 1982 by the CDC
[17] and other investigators [59, 77]. As a consequence the sale
of nitrite inhalants was banned by the US Congress in 1988 (Public
Law 100-690) [58].
Toxicity
of AZT
Although AZT
is an inhibitor of HIV DNA synthesis, it is not a rational medication
for persons with antibodies to HIV for the following reasons: 1)
there is no proof that HIV causes AIDS [33, 36]; 2) since no detectable
RNA-dependent viral DNA synthesis occurs, and since the number of
infected cells remains stable once the virus is neutralized by antibodies
[33, 36], only cell DNA, with or without proviruses of HIV, is terminated
by AZT treatment. Further, since AZT cannot distinguish infected
from uninfected cells and only 1 in 500 T-cells is infected in AIDS
patients and asymptomatic carriers [33, 36, 105], it kills 500 uninfected
cells for every infected cell. Thus AZT is inevitably toxic, killing
500 times more uninfected than infected cells; 3) particularly in
view of the hypothesis that HIV causes AIDS by killing T-cells [62-63,
it is irrational to overkill infected cells with AZT.
As expected
from an inhibitor of DNA synthesis, many studies report AZT-mediated
cytotoxicity. Anemia, neutropenia, and leukopenia occur in 20-50%
with about 30-50% requiring transfusions within several weeks [32,
50, 99, 113, 116]. Severe nausea from intestinal intoxication is
observed in up to 45% [99, 113, 123] and severe muscle atrophy in
6-8% [8, 52, 99, 118]. Acute hepatitis, insomnia, headaches, dementia
seizures, and vomiting are also reported effects of AZT [113]. Lymphomas
appear in about 9% within one year on AZT [94]. AZT is also mutagenic
and carcinogenic in animals [23, 129] and transforms cells in vitro
as effectively as methylcholanthrene [21]. AZT toxicity varies a
great deal with the subject treated, due to differences in kinases
involved in its uptake and in AZT metabolism [21, 39, 113, 130].
Nevertheless,
AZT is thought to have serendipitous therapeutic benefits based
on the only placebo-controlled study of its effects on AIDS patients
[43, 99]. The study was sponsored by Burroughs- Wellcome, the manufacturer
of AZT [43, 99]. In this study T-cell counts were observed to increase
from 4-8 weeks and then to decline to pretreatment levels. Further
AZT was claimed to decrease mortality because only 1 out of 143
in the AZT-treated group died compared to 19 out of 135 in the placebo
group.
However, 30
out of the 143 in the AZT-group depended on multiple transfusions
to survive anemia, compared to only 5 out of the 135 in the placebo
group. Since the number of subjects in the AZT- group who would
have died from anemia if untreated was 30, and thus larger than
the AIDS deaths and anemias of the control group combined 19 + 5,
the claim of decreased mortality is not realistic [43, 99]. Moreover,
66 in the AZT group suffered from severe nausea and 11 from muscle
atrophy compared to only 25 and 3 in the control group. The lymphocyte
count decreased over 50% in 34% of the subjects in the AZT group
and in only 6% of those in the control group. The study is further
comprimised by concomitant medication [99], the failure to consider
the effects of recreational drug use and of patient-initiated randomization
of blinded AZT and placebo treatments [69]. The brief AZT-induced
gain of T-cells may reflect compensatory hemopoiesis and random
killing of pathogenic parasites [39] and the influence of concomitant
medication [99].
Surprisingly,
long-term studies of AZT in animals compatible with human applications
have not been published [113, 130]. In view of the inevitable toxicity
of AZT, its popularity as an anti-HIV drug can only be explained
by the widespread acceptance of the virus- AIDS hypothesis and the
failure to consider the enormous difference between the viral and
cellular DNA targets.
Conclusions
It is concluded
that all American AIDS exceeding the normal low incidence of indicator
diseases in the general population is the result of recreational
and anti-HIV drugs. Thus the American AIDS epidemic is a subset
of the drug epidemic. For example, only the pneumonias, tuberculoses,
and dementias of the 50% of American intravenous drug users with
HIV [86] are recorded as AIDS, while those of their counterparts
are diagnosed by their old names.
Indeed, the
drug-AIDS hypothesis is epidemiologically and pathologically better
grounded than the virus-AIDS hypothesis: about 32% American AIDS
patients are confirmed intravenous drug users, possibly 60% use
recreational drugs orally and an unknown but large percentage of
both behavioral and clinical AIDS risk groups use AZT. Moreover,
the consumption of recreational drugs by AIDS patients is probably
underreported because the drugs are illicit, and because medical
scientists and support for research are currently heavilly biased
in favor of viral AIDS [35, 41, 73]. The toxicity of these drugs
is empirically known for all drugs, and mechanistically for some,
notably for AZT and nitrites.
Nonetheless,
evidence for the role of drugs in AIDS is rejected by proponents
of the virus-AIDS hypothesis [6, 11, 91, 125]. This may be the reason
that despite the current drug use epidemic there are no studies
that investigate the long-term effects of psychoactive drugs and
AZT in animals compatible with the time periods and dosages used
by AIDS patients [73]. Yet, it is a complete mystery how HIV act
as a pathogen, despite enormous research efforts [6, 9, 33, 74,
125], and even antibodies against are confirmed in only about 50%
of AIDS patients [33, 63, 108].
The drug-AIDS
hypothesis resolves all scientific paradoxes posed by the prevailing
virus-AIDS hypothesis.
1) In America
HIV is a long-established, endmic virus, but AIDS is new -- because
the drug epidemic is new.
2) AIDS is
restricted for over 10 years to 10,000 [18] or 0.01% of the over
100 million sexually active heterosexual Americans per year, and
to 20,000 [18] or 0.25% of the 8 million homosexuals, estimated
at 10% of the adult male population [101, 120]. But conventional
venereal diseases are on the rise in the US [5], and there is no
vaccine or drug against HIV. This is because AIDS is due to drug
consumption rather than sexual activity.
3) Over 72%
of American AIDS cases are 20-44-year-old males [18] although no
AIDS disease is male-specific [18, 19, 63] -- because males of this
age group consume over 80% of all hard psychoactive drugs [51, 87].
4) Distinct
AIDS diseases occur in distinct risk groups -- because they use
distinct drugs, eg users of nitrites get Kaposi's sarcoma, users
of intravenous drugs get tuberculosis and users of AZT get leukopenia
or anemia.
5) Viral AIDS
occurs on average 10 years after HIV infection [33, 36, 63], although
infectious agents, as self-replicating toxins, typically strike
within weeks or months after infection [46, 80]. Indeed HIV is immunogenic
and may be mildly pathogenic in humans within weeks after infection
and is then effectively and rapily limited by antiviral immunity
[22, 25]. This is because HIV infection and AIDS are unrelated events.
The duration and toxicity of drug consumption and individual thresholds
for disease determine when AIDS occrrespecitve of when and whether
HIV infec. On average, five to ten years elapse between the first
use of drugs and the need for treatment [31, 40, 54]
6) HIV, as
well as many other parenterally and venereally transmitted microbes
and viruses, are mere markers for AIDS and AIDS risks [27, 33, 45]
-- because the higher the consumption of un- sterile, injected drugs
[28, 40] and sexual contacts mediated by aphrodisiac drugs, the
more microbes are accumulated.
7) Some old
diseases of hemophiliacs, other recipients of transfusions, and
of the general population are called AIDS - because they follow
perinatal or parenteral HIV infection [33].
8) Old African
diseases like slim disease, fever, diarrhea and tuberculosis are
called AIDS now, although they are clinically and epidemiologically
very different from American and European AIDS. They occur in adolescents
and adults of both sexes that are subject to protein malnutrition,
parasitic infections, and poor sanitary conditions [36]. Since HIV
is endemic in over 10% of Central Africans, over 10% of their AIDS
defining diseases will be called AIDS [33, 36, 63].
The drug-AIDS
hypothesis predicts that the AIDS diseases of the behavioral AIDS
risk groups in the US and Europe can be prevented by stopping the
consumption of recreational and anti-HIV drugs, but not by safe
sex [63] and clean injection equipment [86] for unsterile street
drugs. According to the drug-AIDS hypothesis, AZT is AIDS by prescription.
Screening of blood for antibodies to HIV is superfluous, if not
harmful, in view of the anxiety that a positive test generates among
the many believers in the virus-AIDS hypothesis and the toxic AZT
prophylaxis, prescribed to many who test positive. Eliminating the
test would also reduce the cost of the approximately 12 million
annual blood donations in the US [127] by 11 dollars each (personal
communication 1990, Irwin Memorial Blood Bank San Francisco) and
would lift travel restrictions for antibody-positives to many countries
including the US and China. The drug-AIDS hypothesis is testable
epidemiologically and experimentally by studying AIDS drugs in animals.
Note added
in proof
In Europe 33%
of AIDS patients are intravenous drug users and 47% are male homosexuals
and 86% of all patients are male [132].
Acknowledgments
I thank B Ellison
(Berkeley), J Lauritsen (New York), C Pierach (Minneapolis), P Rabinow
(Berkeley), H Rubin (Berkeley, F Rothschild (Berkeley), J Shenton
(London), C Thomas Jr (San Diego), and M Verny-Elliott (London)
for critical information and T Gardner (Santa Barbara) for a generous
donation and encouragment. I am supported by Outstanding Investigator
Grant no 5-R35-CA39915-07 from the National Cancer Institute.
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