Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala
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"HIV", Factor VIII and CD4s
In his rapid response: "Re: More on CD4s", 30 September, Peter Flegg wrote: "They do now give references showing instances where low CD4 counts (<300/microlitre) have occurred in the absence of HIV, and then tag on the suggestion that: "If something decreases the CD4 counts to "less than 300/mcl", there is no reason why it should not decrease then to 50 per microliter." Hmmm…how often would that happen, I wonder? Since I am a physician, I am also meant to know that "if a drug, X, causes an effect, Y, then the magnitude of Y will depend on the dose, the frequency and the duration to which the patient is exposed to X." Well as a physician, I can say very few things in my experience of the human physiological response operates in such a simple, dose-dependent, linear manner, and there are clear limits for most parameters. (If a diuretic can make my serum sodium drop from 130mmol/l to 115mmol/l, will twice the dose make it drop to 100mmol/l, and four times the dose drop it to 70mmol/l?). I am however pleased to have been afforded this insight to the reasoning processes of the Perth Group, as it helps me understand some of their other deductions and conclusions."
We have never claimed that there is a linear relationship between the dose and the effect of drugs. If an agent decreases the CD4 counts to "less than 300/mcl, there is no reason why it should not decrease them to 50 per microliter", even if the "human physiological response" does not operate in "a simple, dose-dependent, linear manner".
Peter Flegg wrote: "Finally, the Perth Groups asks me questions about Montagnier's work in the 1980s, even though these have been conclusively addressed previously by Chris Noble. I refer them to his very competent reply to the topic, which I assume they have not read or understood".
In this debate we have repeatedly asked Christopher Noble's view "about Montagnier's work in the 1980s". Christopher Noble never responded. Even if he did we will still like to know Peter Flegg's view. So, we repeat our request.
Would Peter Flegg please tell us: (1) Does he agree with Gallo's and Montagnier's experimental finding, regarding "HIV" and T4 cells, in which case he must tell them, and thus us, what is wrong with them; (2) Agrees with Gallo's and Montagnier's findings, in which case, he, like us, comes up with an alternative reason for the T4 cell decrease in AIDS patients.
Furthermore, if Peter Flegg thinks we are wrong and in fact very dangerous, then he and Montagnier must write to Medical Hypotheses and refute our critique of Montagnier's work.
Peter Flegg wrote: I do not have any haemophiliac patients with HIV infection, but if I did, I would certainly tell any with CD4 count below 50/mcl that HIV was the cause."
In our paper "Factor VIII, HIV and AIDS in haemophiliacs: an analysis of their relationship"  we wrote: "It is generally accepted that in patients with haemophilia, HIV destroys T4 lymphocytes leading to acquired immune deficiency. Although this view has prevailed for ten years, at least one well known group of researchers of AIDS in haemophiliacs, that from the University of Bonn, questioned the above relationship between HIV and T4 cells as recently as 1990. "It is not clear whether the virus-host interrelationship in HIV infections is regulated primarily by the virus or by the host; i.e., are CD4+ cells depleted by non-viral mechanisms and does the virus adjust itself to the weakened defence? Or is the depletion of CD+ cells the consequence of the spread and cytopathogenicity of virulent viral variants, which developed at random from avirulent precursors?" (Schneweis et al., 1990). Discussing their data a year earlier they concluded "The results suggest that reactivation of HIV occurs when immune deficiency has become manifest" (Schneweis et al, 1989). The question whether HIV leads to T4 cell depletion or conversely whether T4 cell depletion leads to "HIV infection" (particles, RT in cultures, antigen/antibody reactions, "HIV/PCR") can only be resolved by having direct evidence that HIV destroys the T4 cells of haemophiliacs. No such evidence exists. An indirect method of resolution is the examination of the chronological sequence of HIV infection and T4 cell depletion. Numerous reports from many well known researchers of AIDS in haemophiliacs have shown that T4 cell depletion precedes "HIV infection".
1. Mortimer and his colleagues state, "The OKT4 subset was reduced in both seropositive (p < 0.01) and seronegative (p < 0.05) haemophiliacs but there was no difference between seropositive and seronegative patients" (Moffat, Bloom & Mortimer, 1985);
2. Weiss and colleagues report, "We have thus been able to compare lymphocyte subset data before and after infection with HTLV-III. It is commonly assumed that the reduction in T-helper-cell numbers is a result of the HTLV-III virus being tropic for T-helper-cells. Our finding in this study that T-helper-cell numbers and the helper/suppressor ratio did not change after infection 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" (Ludlam et al, 1985);
3. Kessler and colleagues found, "Repeated exposure to many blood products can be associated with development of T4/T8 abnormalities" including "significantly reduced mean T4/T8 ratio compared with age and sex-matched controls" (Kessler et al, 1983);
4. In 1984, Tsoukas et al observed that among a group of 33 asymptomatic haemophiliacs receiving factor VIII concentrates, 66% were immunodeficient "but only half were seropositive for HTLV-III", while "anti-HTLV-III antibodies were also found in the asymptomatic subjects with normal immune function". They summarised their findings as follows: "These data suggest that another factor (or factors) instead of, or in addition to, exposure to HTLV-III is required for the development of immune dysfunction is haemophiliacs" (Tsoukas et al, 1984);
5. By 1986 researchers from the CDC concluded: "Haemophiliacs with immune abnormalities may not necessarily be infected with HTLV-III/LAV, since the factor concentrate itself may be immunosuppressive even when produced from a population of donors not at risk for AIDS" (Jason et al, 1986);
6. In 1985 Montagnier (Montagnier, 1985) wrote: "This [clinical AIDS] syndrome occurs in a minority of infected persons, who generally have in common a past of antigenic stimulation and of immune depression before LAV infection".
Who is right and who is wrong? Peter Flegg or Weis, Ludlam, the CDC and Montagnier?
1. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Causer D. Factor VIII, HIV and AIDS in haemophiliacs: an analysis of their relationship. Genetica 1995;95:25-50. http://www.theperthgroup.com/SCIPAPERS/ephemophilia.html
Competing interests: None declared