Page Comparison

...

...

Abstract

Our analysis of drug use and morbidity data from a cohort of 1034 men yields the following results: 1) HIV infection  is a strong indicator of drug use - HIV-positive respondents reported an average lifetime dose of recreational drugs  (excluding marijuana) 2.3 times higher than HIV-negative respondents. 2) Homosexuality is a strong indicator  of drug use - homosexual respondents reported an average lifetime dose 2.0 times higher than heterosexual  respondents. 3) The incidence of AIDS-defining diseases was not limited to respondents infected with HIV, but  was almost completely limited (98%) to respondents who reported using drugs.-We also address a previous report  (Ascher et al., 1993) that was based on the same database and purported to show that HIV alone correlates with  the development of AIDS. Specifically, we show that the relationship between HIV infection and CD4+ T Cell loss  is weaker than reported by Ascher et al., and provides little evidence for a causative relationship. These results  support the hypothesis that long-term, habitual drug use can cause the conditions known as AIDS (independent of  the presence of HIV), and refute the hypothesis that HIV alone causes these conditions independent of drug use.

Introduction  

A Nature Commentary by Ascher et al. purported to show that infection by the human immunodeficiency virus (HIV)alone correlates with the development of the acquired immune deficiency syndrome (AIDS)  (Ascher et al., 1993). According to their analysis of the San Francisco Men's Health Study (SFMHS), drug  use had no effect on T cell loss over time, while all cases of AIDS and all T cell depletion occurred among  HIV-positive men. Ascher et al. interpret this apparent correlation between HIV and AIDS as support for 'the well-established causal relationship between HIV and  AIDS' (Ascher et al., 1993).  

...

In addition to reviewing the data cited by Ascher et al., we were also able to perform our own analysis of the primary data. This paper presents some of our findings. Despite the extremely sparse reporting of AIDS  indicator diseases in the database, we found 45 cases of these diseases among HIV negative respondents. Also,  we quantified a higher level of drug use among HIV positive men than among their HIV negative counterparts. These results suggest a direct link between drug use and AIDS independent of HIV infection.  

The SFMH Study

The SFMHS is a population-based longitudinal survey of 1034 men, recruited in 1984 from the San Francis- co precincts most heavily populated with homosexual men. (For reasons unknown to us, Ascher et al. used only 1027 of these men in their analysis). Of these subjects, 816 identified themselves as homosexual or bisexual and 215 as heterosexual. At the end of the study's seventh year, 578 men remained HIV nega- tive, 46 had seroconverted, 400 had entered the study already seropositive, and 10 remained undetermined; 215 men had been officially recorded with diagnoses of AIDS. Data are collected by semi-annual interviews, which tabulate such self-reported data as medical con- ditions, use of pharmaceutical or recreational drugs, and a number of other responses that are difficult to verify.

...

We shall document these and other defects of the SFMHStudy as well as of the Commentary by Asch- er et al. based on that study. Our analysis will show that Ascher et al.'s claim that 'the population-based SFMHS provides a rigorously controlled epidemiolog- ical model for the evaluation of aetiological hypothe- ses' is unjustified (Ascher et al., 1993).

The Ascher et aL Commentary

The Commentary reported a perfect association between HIV and AIDS, as well as between HIV and a progressive decline in CD4+ T cells. It also found no relationship between drug use and T cell loss. But the analysis suffers from several logical flaws:

...

3) The hypothesis of drug use as the cause of AIDS is analogous to the cigarette-smoking hypothesis of lung cancer and the alcohol hypothesis of liver cirrho- sis (Lauritsen & Wilson, 1986; Duesberg, 1992). That is, disease symptoms depend primarily on the lifetime dose of the relevant drug, a function of both quantity and number of years of consumption. Thus a proper longitudinal study would quantify each respondent's total lifetime drug use. Ascher et al. imply that they have done this: "We examined the cohort at 6-monthly [sic] intervals for 96 months, and obtained drug-use data and determined HIV serostatus at each examina- tion" (Ascher et al., 1993). But in the Commentary, all study subjects were stratified according to a single drug use report, taken during the first wave of the study. Fur- thermore, although the respondents were asked about use of nine to ten different psychoactive drugs (see below), only four of those drugs were incorporated into the paper's analysis. Moreover, no mention was made of AZT, the toxic and immune-suppressive DNA nucleoside analogue prescribed as AIDS therapy.

Our analysis of the data and our results

Statistical tests are based on Cochran and Cox t-tests (with unequal variances), or on univariate linear regression.

...

c) Much of the drug use data is missing from the study altogether. Only 17% of the respondents answered all drug use questions during the first seven years; 22% of the respondents answered half or fewer of the questions. Furthermore, there is a strong negative correlation between reported level of drug use and number of responses to drug use questions (sloPe = -1.76 + 0.32, p < 0.0001), meaning that those subjects who responded the fewest times claimed the highest average drug use. This result indicates that men using the most drugs were least reliable in their responses.

Conclusions

Table3. Average doses of drugs(other than marijuana) per year, HIV+ vs. HIV- and homosexuals vs. heterosexuals.

...

Further results might possibly still be extracted from the SFMHS database, including an analysis of the effects of AZT; of the 400 seropositive men in the study, 215 (54%) reported use of this DNA chain- terminating chemotherapy. But an epidemiological study of the causality of AIDS, controlling for both HIV and lifetime drug exposure, will require some other more adequate cohort. From the standpoint of biological plausibility, the toxicity of long-term drug use makes much more sense as a damaging agent to the immune system than do the 'enigmatic mechanisms' of the conventional retrovirus HIV (Ascher et al., 1993).

Acknowledgements

We are indebted to Warren Winkelstein, Jr., for providing access to the data from the SFMHS study, and to Eric Vittinghoff for technical assistance. We also thank Phillip Johnson, Richard Strohman, Malcolm Zaretsky, John Lauritsen, Charles A. Thomas, Steve Smale, and Harvey Bialy for critical reviews. Supported in part by the Council for Tobacco Research, USA, and private donations from Glenn Braswell (Los Angeles, Calif., USA), Dr. Richard Fischer (Annan- dale, Va., USA), Dr. Fabio Franchi (Trieste, Italy) and Dr. Friedrich Luft (Berlin, Germany).

References

• Ascher, M.S., H.W. Sheppard, J. Winkelstein, & E. Vittinghoff, 1993. Does drug use cause AIDS? Nature (London) 362:103-4.

• CentersforDiseaseControl, 1987.Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. J. Am. Med. Assoc. 258:1143-1154.

• Centers for Disease Control, 1993. HIV/AIDS Surveillance; year-end edition. February Issue.

• Centers for Disease Control and Prevention, 1992. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb. Mort. Weekly Rep. 41:1-19. Duesberg, P., 1992. AIDS acquired by drug consumption and other noncontagious risk fac- tors. Pharmacology & Therapeutics 55:201-277.

• Duesberg, P.H., 1992. AIDS Acquired by Drug Consumption and Other Noncontagious Risk Factors, Pharmac. Ther. Vol. 55 pp. 201-277.

• Duesberg, P., 1993a. The HIV gap in national AIDS statistics. Biotechnology 11:955-956.

• Duesberg, P.H., 1993b. Can epidemiology determine whether drugs or HIV cause AIDS? AIDS-Forschung 12:627-635.

• Friedman-Kien, A.E., B.R. Saltzman, Y. Cao, M.S. Nestor, M. Mirabile, J.J. Li & T.A. Peterman, 1990. Kaposi's sarcoma in HIV-negative homosexual men. Lancet 335:168-169.

• Haverkos, H.W., 1988. Epidemiologic studies - Kaposi's sarcoma vs. opportunistic infections among homosexual men with AIDS. In: Health Hazards of Nitrite Inhalants, Research Monograph 83, pp. 96-105, H.W. Haverkos & J.A. Dougherty (eds.) National Institute on Drug Abuse, Rockville, MD.

• Haverkos, H.W. & J.A. Dougherty (eds) (1988) Health Hazards of Nitrite Inhalants. NIDA Research Monograph 83, National Institute on Drug Abuse, Washington DC.

• Holt, P.G., L.M. Finlay-Jones, D. Keast & J.M. Papadimitrou, 1979. Immunological function in mice chronically exposed to nitrogen dioxide (NO2). Environmental Research 19: 154-162.

• Institute of Medicine and National Academy of Sciences, 1986. Confronting AIDS. National Academy Press, Washington, DC.

• Jaffe, H.W., K. Choi, P.A. Thomas, H.W. Haverkos, D.M. Auerbach, M.E. Guinan, M.E Rogers et aL, 1983. National case-control study of Kaposi's sarcoma and Pneumocystic carinii pneumonia in homosexual men: Part 1, epidemiologic results. Ann. Intern. Med. 99:145-151.

• Lang, W., R.E. Anderson, H. Perkins, R.M. Grant, D. Lyman, W. Winkelstein, R. Royce & J.A. Levy, 1987. Clinical, immunologic, and serologic findings in men at risk for Acquired Immunodeficiency Syndrome. J. Am. Med. Assoc. 257:326--330.

• Lauritsen, J. & H. Wilson, 1986. Death Rush, Poppers and AIDS. Pagan Press, New York.

• Murray, H.W., D.A. Scavuzzo, C.D. Kelly, B.Y. Rubin & R.B. Roberts, 1988. T4+ cell production of interferon gamma and the clinical spectrum of patients at risk for and with acquired immunodeficiency syndrome. Arch. Intern. Med. 148:1613- 1616. Newell, G.R., M.R. Spitz & M.B. Wilson, 1988. Nitrite inhalants: Historical perspective. In: Health Hazards of Nitrite Inhalants, Research Monograph 83, pp. 1-14, H.W. Haverkos and J.A. Dougherty (eds.) National Institute of Drug Abuse, Rockville, MD.

• Ortiz, J.S.&V.L.Rivera, 1988. Altered T-cell helper/suppressor ratio in mice chronically exposed to amyl nitrite. In: Health Hazards of Nitrite Inhalants, Research Monograph 83, pp. 59-74, H.W. Haverkos and J.A. Dougherty (eds.) National Institute on Drug Abuse, Rockville, MD.

• Schechter, M.T., KJ.P. Craib, K.A. Gelmon, J.S.G. Montaner, T.N. Le & M.V. O'Shaughnessy, 1993. H1V-1 and the aetiology of AIDS. The Lancet 341:658-659. Spornraft, P., M. Froschl, J. Ring, M. Meurer, F.D. Goebel, H.W. Ziegler-Heitbrock et al., 1988. T4/T8 ratio and absolute T4 cell numbers in different clini- cal stagesof Kaposi's sarcoma in AIDS. Br. J. Dermatol. 119:1-9.