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.

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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