Continuum volume 5, number 5 - mid-winter 1999
(a) there was no evidence that retroviruses kill cells, to the contrary;
(b) many factors to which patients belonging to the AIDS risk groups are exposed are immunosuppressive. This fact was known to some of the best known HIV experts. In 1985 Montagnier wrote: "This syndrome [the AIDS diseases] occurs in a minority of infected persons, who generally have in common a past of antigenic stimulation and of immune depression before LAV [HIV] infection",1. In the same year Weiss, Ludlam and their associates wrote (concerning patients with haemophilia): "Our finding...supports our previous conclusion that the abnormal T-lymphocyte subsets are a result of the intravenous infusion of Factor VIII concentrates per se, not HTLV-III infection",2. One year later researchers from CDC: "...factor concentrate [Factor VIII] itself may be immunosuppressive even when produced from a population of donors not at risk for AIDS" ,3 ;
(c) evidence also existed that many factors including infections, and trivial ones, such as exposure to the sun or radiation in solaria lead to decreased T4 cells. Although some of the T4 decreases were long lasting, the patients did not develop KS and OI;4 a significant proportion of the "AIDS" patients, including patients with KS and OI infections, had normal numbers of T4 cells.4 In other words, T4 decrease (immune deficiency) is neither necessary nor sufficient for the development of KS and OI. Thus the proposition that KS and the OI are the result of T4 decrease and that the T4 decrease detected in the patients belonging to the AIDS risk groups was caused by HIV infection was totally inconsistent with the data available even before the hypothesis was put forward. For some time now, all HIV/AIDS experts, including Robert Gallo, accept that HIV has no direct or indirect role in KS.5-7
The HIV theory predicted that HIV was sexually transmitted and therefore AIDS would spread throughout the heterosexual population. Obviously this has not happened. The prediction by proponents of the HIV theory that a vaccine would be developed by 1986 also has not been fulfilled. In 1984 Montagnier said that the only way to prove HIV is the cause of AIDS is to have an animal model.8 Although no effort has been spared, no model of a retrovirus causing AIDS has been forthcoming. Indeed, the only animal model that bears any resemblance to human AIDS fully supports a non-infectious modus operandi.9
WHAT LED A PHYSICIST TO STUDY AIDS
At the outbreak of AIDS, Gallo had
already spent a decade in attempts to prove that the cause of some
cancers was a retrovirus. This led him to put forward the
retroviral theory of AIDS. From an equally biased position I put
my non-infectious theory. Although trained as a nuclear physicist,
with the exception of a few years, I have worked in the medical
field in the Department of Medical Physics of the Royal Perth
Hospital, the largest teaching hospital in Western Australia.
Among its many activities it was involved in treating cancer by
radiation and pioneered hyperthermia for the same purpose.
The theory claimed that the
cellular redox level and its oscillations, that is, the cyclic
variation between oxidation and reduction, plays a pivotal role in
both normal and abnormal cellular function and structure. Diseases
such as cancer, cardiovascular, clotting abnormalities and ageing,
for example are the result of perturbation of the cellular redox
level and its oscillations.
PREDICTION OF THE OXIDATIVE STRESS THEORY OF AIDS
The predictions of my theory
In 1985 Montagnier and his colleagues reported that the wife of a haemophilia man who, in addition to other sexual acts, practised anal intercourse was found to have a positive antibody test and low numbers of T4 cells. "During 10 months of follow-up his wife remained clinically well, discontinued exposure to semen, and then lost the LAV antibody, and regained a normal number of T-helper cells" (T4 cells).12
The best and largest study, the Multicenter AIDS Cohort Study of 4995 gay men, which commenced in 1984 and is still ongoing, also confirmed this in 1987. "Receptive anal intercourse accounted for nearly all new HIV infections among the homosexual men enrolled in this study, and the hazards of this practice need to be emphasised in community educational projects".13
In a review of most, if not all,
epidemiological studies conducted in gay men published in 1994,
the authors concluded: "it can be said that the cited reports
yield convincing evidence that:
Unquestionably, to date, the best
designed and executed study in heterosexuals was conducted by
Nancy Padian and her associates. In a paper entitled
"Male-to-Female Transmission of Human Immunodeficiency Virus"
published in 1987 wrote:
Thus, a positive antibody test and
AIDS, like pregnancy, can be sexually acquired but not sexually
transmitted. The difference is, that while pregnancy can be
acquired by a single sexual intercourse, for AIDS to appear a very
high frequency of receptive intercourse over a long period is
absolutely necessary. AIDS is more like cervical cancer. The
effect is not the result of the act itself, but its high
frequency. But, as with pregnancy and cervical cancer, other
factors may mitigate against the development of AIDS.
One year later, in an article
published in the British Medical Journal, one reads,
"Intravenous drug abusers appear to be at special risk of
acquiring tuberculosis, and a high rate of infection in this group
was reported well before AIDS began".18
In 1994, researchers from Switzerland reported their findings from a prospective study designed "to examine differences in the incidence and spectrum of diseases comprising 314 HIV-seronegative NDU, 217 HIV-seropositive NDU, and 10 NDU with admissions registered in either group (from a total of 1011 admissions)". Narcotic drug users (NDU) were enrolled in the study if "they were hospitalised for a minimum of 24 hrs, and also presented with at least one of the following characteristics: history of either parenteral drug use or a corresponding oral substitutive medication (mainly methadone); or actual intoxication and miosis [pinpoint pupils] responding to naloxone; or opiate or cocaine metabolites in a urine sample. Individuals with exclusive oral drug use other than opiates were not included". "HIV- seropositive NDU were more frequently admitted for infectious complications or various non-infectious medical complications (including as most frequent cases, 38 admissions for ill-defined episodes, 11 for repeated seizures, nine for acute pancreatitis, and six for adverse medical drug reaction). Moreover, they also tended to have a higher admission incidence density for intoxication, whereas there was no difference in admissions for suicide tentative or withdrawal reaction". However, individuals from both groups, seropositive and seronegative were admitted for "infectious complications", including non-opportunistic pneumonia, purulent bronchitis, tuberculosis, soft tissue infection, osteoarticular infection, endocarditis, primary bacteremia and disseminated candidiasis. More importantly, of a total of 541 admissions of seropositive individuals, 187 (35%) were individuals who had an ORAL mode of drug "application" and 9 (0.5%) inhalation.20
That both intravenous and oral drug users develop positive "HIV" antibody tests was shown as far back as 1988 when Sterk reported that a higher percentage of prostitutes who use oral drugs (84%), than IV (46%), test positive.21
In another study published in 1993, researchers from New York City tested 1246 seronegative drug users. "Nine had at least one CD4 cell count of <300 cells/ml or a CD4<20%" and 21 subjects "had one CD4 cell count between 300 and 500 cells/ul". They also reported that "CD4 cell counts of <500 cells/ul were, however, associated with subsequent HIV seroconversion...The relative risk for seroconversion among subjects with one or more CD4 count <500 cells/ul, compared with HIV-negative subjects with all counts >500 cells/ul was 4.53"...consistent with an Italian study showing IDU's with CD4 counts <1,000/ul were more likely to seroconvert"22. (The authors of the latter reported a "low number of T4 cells was the highest risk factor for HIV infection" (relative risk=8.5)23. In other words, in drug users, a decrease in T4 cells instead of following seroconversion is a predictor for seroconversion, a finding completely at odds with the HIV theory of AIDS.
(4) In Africa there was neither a new disease AIDS nor a new virus HIV. When Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? as finally published was written in 1984/85, Africa was not considered an important issue. Thus, Africa is only briefly mentioned. Following the 1986 Paris AIDS conference, AIDS in Africa became the defining example of heterosexual transmission. This is the reason that my paper was initially rejected by Medical Hypotheses. The March 1987 letter of resubmission was accompanied by a 12 page document entitled "AIDS in Africa and its heterosexual transmission". This included the following summary:
The data from Africa used to prove heterosexual transmission will not stand up to even superficial scientific analysis". The detail of the text included:
The final section examined the
evidence for heterosexual transmission of AIDS in Africa and
concluded that "we are left with a sexually transmitted disease
(5) The theory also predicted that decrease in T4 cells is not the hallmark of either HIV infection or the clinical syndrome, that is, the decrease in T4 cells is not HIV specific and is neither necessary nor sufficient for the syndrome to appear, that is, the clinical syndrome is not the result of immune deficiency. In fact it was postulated that the decrease in T4 cells may not be due to their destruction by HIV or any other agent but could result from (i) the extreme sensitivity of T cells to oxidative stress; (ii) T4 cells possessing a lower negative charge than T8 cells could be the first to be destroyed by persistent oxidative stress; (iii) to be sequestrated in diseased peripheral tissues; (iv) decreased binding of the T4 antibody as a result of changes in their surface, that is, due to "down regulation" of the CD4 receptor. To illustrate that at present this is accepted even by HIV/AIDS experts it suffices to quote two papers published last year and one more recently:
"This article discusses the
importance of alterations in the CD4+ and CD8+ cell migration in
regulating blood lymphocyte levels and questions the extent of
virus-mediated CD4+ cell destruction";26 "Along with
other recent analyses and experimental developments these
considerations also suggest a need to re-evaluate current concepts
about HIV pathogenesis, including the concept that a systemic
depletion of CD4+ T cells is the hallmark of the
(6) A most important prediction was that the tissues of AIDS patients and those at risk would be oxidised, in general, and in particular they would have low sulphydryl (-SH) group levels. In recent years there have been hundreds of papers confirming this prediction. The first was published by German researchers who, for reason(s) not stated, undertook experiments to determine the level of reduced thiols (-SH) in the blood of "HIV" infected individuals. They found that: "Blood plasma samples from HIV-1 infected persons contain elevated glutamate concentrations up to 6-fold the normal level and relatively low concentrations of acid-soluble thiol (i.e. decreased cysteine concentrations). The intracellular glutathione concentration in peripheral blood-mononuclear cells (PBMC) and monocytes from HIV antibody-positive persons are also significantly decreased",29. Last year a book published with Luc Montagnier as principal editor further confirms the involvement of oxidative stress in AIDS,30.
(7) The 10th of July 1986 letter of re-submission to Nature was accompanied by a response to the reasons given by the Journal for rejection. The response ended with the following: "If my paper does nothing other than draw attention to the oxidative nature of the risk factors and its biological importance, then it offers what is so far the only hope of treatment which will arrest and reverse the otherwise invariable fatal course of the disease. In my opinion this alone would more than justify its publication".
Indeed the most important practical prediction of the theory was that AIDS can be prevented and treated by stopping exposure to the oxidising risk factors and by using "currently available therapeutic [antioxidants in general and SH-containing, in particular] substances". The best confirmation of this comes from researchers at Stanford University, USA. In 1997 discussing their results they wrote: "In essence, we have shown that GSH levels are lower in subjects with CD4 T cell counts below 200/ml (CD4 <200) than in subjects at earlier stages of HIV disease; that among subjects with CD4 <200, lower levels of GSB (a FACS measure of GSH in CD4 T cells) predict decreased survival; and that the probability of surviving 2-3 years increases dramatically as GSB levels approach normal range. In addition, we have presented preliminary evidence suggesting that oral administration of NAC, which supplies the cysteine required to replenish GSH, may be associated with improved survival of subjects with very low GSH levels" (GSH-reduced glutathione),31.
Last year they stated: "We have shown that GSH depletion is associated with impaired survival; the greater the depletion, the worse the prospects for survival...By replenishing GSH, NAC or other agents we may be able to modulate such adverse effects of GSH depletion",30. However, although the authors are most probably aware of our work (the publications of the Perth group were sent to them a few years ago and are indexed in the Medlines under oxidative stress), for some unknown reason, they state: "HIV-infected individuals would be better served if we could identify the mechanism that underlines the GSH depletion and intervene, if possible, to prevent its occurrence". The best advice they can give in this regard is: "it may be prudent for those individuals to avoid excessive exposure to UV irradiation and unnecessary use of drugs that can deplete GSH - e.g., alcohol and prescription or over-the-counter formulations containing acetominophen [paracetamol]".
(6) Perhaps the boldest claims and predictions were made regarding the existence of HIV. I wrote HIV, "has never been isolated from fresh AIDS tissues". Furthermore, HIV "has never been isolated as an independent stable particle". That is, HIV had not been isolated from either fresh tissues or culture, which means that its existence had not been proven and this situation has not changed up to the present day. At least Montagnier in his 1997 interview to Djamel Tahi admitted that he had not isolated HIV and in his view neither had Gallo,32. I presented evidence that the observed phenomena (particles, reverse transcriptase, antibody/antigen reactions) which were said to prove the existence of HIV were not specific to a specific retrovirus nor even to retroviruses in general. Unlike Gallo, Montagnier when interviewed by Djamel Tahi, eventually reluctantly admitted that these phenomena were not retrovirus specific. I cited examples of evidence which, taken together, led to the conclusion that oxidising agents were causing not only AIDS but also gave rise to the phenomena which were interpreted by the Montagnier and Gallo school as indicating the presence of HIV. As far back as 1986 Montagnier knew that the phenomena could not be obtained unless the cultures were stimulated, although he did not know that the stimulants were oxidising agents,33. In 1991 Anthony Fauci proved that the "HIV" phenomena could be inhibited by antioxidants,34.
It is over twenty years since I conceived the redox theory of cellular function and nearly as long since its specific application to the problem of AIDS appeared in Medical Hypotheses. I look back over this time with very mixed feelings. Naturally I am proud that as a scientific theory every prediction concerning AIDS has materialised. However, I am saddened that there are forces at work which have consistently prevented purposeful but friendly debate. To me and my group the problematic nature of the HIV theory was apparent from the very beginning. It is now my fervent hope that, as the HIV theory continues to fail the many patients who are diagnosed with antibodies to "HIV" and AIDS, the time is rapidly approaching when scientists and physicians will be eager to examine our contribution.
1. Montagnier L. (1985). Lymphadenopathy-Associated Virus: From Molecular Biology to Pathogenicity. Ann. Int. Med. 103:689-693.
2. Ludlam CA, Steel CM, Cheingsong-Popov R, et al. (1985). Human T- Lymphotropic Virus Type-III (HTLV-III) Infection in Seronegative Haemophiliacs after Transfusion of Factor VIII. Lancet II:233-236.
3. Jason JM, McDougal JS, Dixon G, et al. (1986). HTLV-III/LAV Antibody and Immune Status of Household Contacts and Sexual Partners of Persons with Haemophilia. JAMA 255:212-215.
4. Papadopulos-Eleopoulos E, Turner VF, Papadimitriou JM, Hedland- Thomas B, Causer D, Page B. (1995). A critical analysis of the HIV-T4- cell-AIDS hypothesis. Genetica 95:5-24.
5. Papadopulos-Eleopulos E. (1988). Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? Med. Hypotheses 25:151-162.
6. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. (1992). Kaposi's sarcoma and HIV. Med. Hypotheses 39:22-9.
7. Lauritsen JL. NIDA meeting calls for research into the poppers-Kaposi's sarcoma connection. (1995). p. 325-330 In: AIDS: Virus- or Drug Induced Duesberg PH, ed Kluwer Academic Publishers, London.
8. Vilmer E, Rouzioux C, Vezinet Brun F, et al. (1984). Isolation of new lymphotropic retrovirus from two siblings with Haemophilia B, one with AIDS. Lancet I:753-757.
9. Ter-Grigorov VS, Krifuks O, Liubashevsky E, Nyska A, Trainin Z, Toder V. (1997). A new transmissible AIDS-like disease in mice induced by alloimmune stimuli. Nat. Med. 3:37-41.
10. Goedert JJ, Sarngadharan MG, Biggar RJ, et al. (1984). Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men. Lancet 2:711-6.
11. Stevens CE, Taylor PE, Zang EA, et al. (1986). Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City. JAMA 255:2167-2172.
12. Burger H, Weiser B, Robinson WS, et al. (1985). Transient antibody to lymphadenopathy-associated virus/human T-lymphotropic virus type III and T-lymphocyte abnormalities in the wife of a man who developed the acquired immunodeficiency syndrome. Ann. Int. Med. 103:545-7.
13. Kingsley LA, Kaslow R, Rinaldo CR, et al. (1987). Risk factors for seroconversion to human immunodeficiency virus among male homosexuals. Lancet i:345-348.
14. Caceres CF, van Griensven GJP. (1994). Male homosexual transmission of HIV-1. AIDS 8:1051-1061.
15. Padian N, Marquis L, Francis DP, et al. (1987). Male-to-female transmission of human immunodeficiency virus. JAMA 258:788-90.
16. Padian NS, Shiboski SC, Glass SO, Vittinghoff E. (1997). Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am. J. Epidemiol. 146:350-357.
17. Layon J, Warzynski M, Idris A. (1986). Acquired immunodeficiency syndrome in the United States: a selective review. Critical Care Medicine 14:819-27.
18. Goldman KP. (1987). AIDS and tuberculosis. Brit. Med. J. 295:511-512.
19. Des Jarlais DC, Friedman SR. (1994). AIDS and the use of injected drugs. Sci. Am. 56-62.
20. Scheidegger C, Zimmerli W. (1996). Incidence and spectrum of severe medical complications among hospitalised HIV-seronegative and HIV-seropositive narcotic drug users. AIDS 10:1407-14.
21. Sterk C. (1988). Cocaine and HIV seropositivity. Lancet i:1052-1053.
22. Des Jarlais DC, Friedman SR, Marmor M, et al. (1993). CD4 lymphocytopenia among injecting drug users in New York City. J. Acquir. Immun. Defic. Syndr. 6:820-822.
23. Nicolosi A, Musico M, Saracco A, Molinari S, Ziliani N, Lazzarin A. (1990). Incidence and risk factors of HIV infection: A prospective study of seronegative drug users from Milan and Northern Italy, 1987-1989.Epidemiology 1:453-459.
24. De Cock KM, Soro B, Coulibaly IM, Lucas SB. (1992). Tuberculosis and HIV infection in sub-Saharan Africa. JAMA 268:1581-7.
25. Kashala O, Marlink R, Ilunga M, et al. (1994). Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1cross-reactivity and antibodies to lipoarabinomannan. J. Infect. Dis. 169:296-304.
26. Rosenberg YJ, Anderson AO, Pabst R. (1998). HIV-induced decline in blood CD4/CD8 ratios: viral killing or altered lymphocyte trafficking? Immunol.Today 19:10-7.
27. Grossman Z, Herberman RB, Vatnik N, Intrator N. (1998). Conservation of total T-cell counts during HIV infection: alternative hypotheses and implications. J. Acq. Immune Def. Syndr. Hum. Retrovirol. 17:450-7.
28. Hellerstein M, Hanley MB, Cesar D, et al. (1999). Directly measured kinetics of circulating T lymphocytes in normal and HIV-1 infected humans.Nat. Med. 5:83-89.
29. Eck HP, Gmunder H, Hartmann M, Petzoldt D, Daniel V, Droge W. (1989).Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients. Biol. Chem. Hoppe-Seyler 370:101-8.
30. Montagnier L, Olivier R, Pasquier C, eds. Oxidative stress in cancer,AIDS and neurogenerative diseases. New York: Marcel Dekker Inc, 1998.
31. Herzenberg LA, De Rosa SC, Dubs JG, et al. (1997). Glutathione deficiency is associated with impaired survival in HIV disease. Proc. Natl. Acad.Sci. U S A 94:1967-72.
32. Tahi D. (1998). Did Luc Montagnier discover HIV? Text of video interview with Prof. Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 5:30-34.
33. Klatzmann D, Montagnier L. (1986). Approaches to AIDS therapy. Nature 319:10-11.
34. Kalebic T, Kinter A, Poli G,
Anderson ME, Meister A, Fauci AS. (1991). Suppression of human
immunodeficieny virus expression in chronically infected monocytic
cells by glutathione, glutathione ester, and N-acetylcysteine.
Proc. Natl. Acad. Sci. U S A 88:986-990.
Continuum volume 5, number 5 - mid-winter 1999