Re: Aids and the making of the Public Mind 13 October 2004
Previous Rapid Response Next Rapid Response Top
Nicholas Bennett,
Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY

Send response to journal:
Re: Re: Aids and the making of the Public Mind

My light-hearted, if wearily tongue-in-cheek, contribution to the debate was sent many hours before I was even aware of Mr Russel's. I was in the process of forming a reply when he jumped the gun: and I would request an apology if I thought one would be forthcoming. Actually, the editors should have been aware of the timing and simply rejected the rather venomous contribution, but I digress.

As much as I admire Ms Winfrey as a canny businesswoman and talkshow host, I hesitate to take my health advice from her, and an abridged lecture in International Communication.

After billions of dollars (and pounds, and yen, and francs...) we are beginning to get a pretty good grasp of the pathogenic mechanisms of HIV and AIDS. See my recent post on the subject of October 2nd.

I'm impressed at the simultaneous damning and acceptance of epidemiology, upon which all clinical trials are built. Every drug in existence is, fundamentally, accepted or rejected based on epidemiological data. Disease risk factors from cancer to stroke are discovered, tested, confirmed and refuted through epidemiological studies. In many ways clinical medicine is founded upon and grows with epidemiology. As much as I dislike admitting it, my exciting contributions to the molecular biology of the virus are exceedingly small fry and unlikely to contribute much to curing AIDS. The sexual nature of the infection was suggested and confirmed by several studies, some of which are even quoted as proof that HIV cannot be sexually transmitted! Low rates do not mean no rates. The fact that female sexual partners of gay men, or sexual partners of IV drug users developed HIV infection and AIDS, was one of the early key pointers away from drugs or lifestyle and towards a sexually transmitted infection [1].

There is a very simple explanation for the differences between the expectations and the outcome. In the mid 1980s people with AIDS were living under a year after being discovered. Once HIV testing became more widespread, it became more obvious that HIV infection could be long-lived: therefore the initial fears that infection would lead to rapid death were unfounded, except in a few cases. The average untreated progression time is 8-10 years. However, such widespread media coverage lead to changes in sexual behaviour that may well have limited the spread of HIV - I recall seeing teenage advice columns where the hysteria was such that people thought the mere act of intercourse somehow created HIV. I agree that STD rates and, in some countries, teenage pregnancies are rising, whereas HIV rates may be static or dropping. This is no surprise if we see that the STDs are in teenage heterosexuals and the HIV rates are in gay men. Due to the nature of sexual relations, mixing between groups is relatively uncommon and divisions like this are expected. For the same reason it explains the lower (but not lack of) spread to women in the developed world, except among IV drug users. HIV does not discriminate, but people do... A highly similar profile is seen with hepatitis B and C transmission: Hep C in fact is almost exclusively blood-borne, and therefore "discriminates" against non-IV drug users. It's not rocket science!

HIV transmission can be demonstrated in animal models (the same animal models that some like the Perth Group claim do not exist) [e.g. 2- 4). The HIV types that are transmitted are nearly always of the type that infect macrophages rather than T cells, suggesting a strong limit to infection occuring at mucosal layers. Prostitutes with anti-HIV cellular immune responses are protected from infection, but if they lose these responses they become infected [5]. Blood of AIDS patients can contain several thousand tissue-culture infectious doses per ml (hardly a low value) [6]. Quantitative measures of HIV in semen have been performed using DNA, RNA and Culture assays: the level of HIV depends on whether or not the patient is treated and the presence of other ongoing infections [7]. HIV can also be detected in cervico-vaginal secretions [8]. There is plenty of evidence to suggest and support a sexual mode of transmission! If only people like Mr Russel would stop believing the misinformation scattered over the internet. It is all to easy to say "X isn't true, therefore..." and the lies are lost from the fourth word of the sentence. This is the general format of pseudoscientific statements: to state a falsehood and then build an argument upon it. The oxidative stress theory of holes in the head is an illustration of the pseudoscience principles being applied to a more easily understood concept than that of HIV pathogenesis. It is, as Mr Russel, points out, drivel - which is what I propose is a good description of the oxidative stress theory of AIDS.

The "lentivirus" as a clinical/structural classification is no longer appropriate, but nowadays is still used as a genetic classification. HIV is far from a conventional retrovirus: conventional retroviruses have 3 genes (Gag Pol Env). HIV has 9 (Gag Pol Env Tat Rev Nef Vif Vpu Vpr) - this puts it into the "complex" retrovirus classification, which includes the Lentivirus genus. The prototypical lentivirus in fact isn't even human - maedi visna virus, in sheep. Aside from the old onco-, lenti-, spuma- virus classification, the more recent A, B, C, and D type classification has been modified also in recent years: based as it was on EM visual appearance and not the actual genetic relationship of the viruses. Under the new classification, some classical "lentiviruses" such as HTLV are no longer called that even though the original meaning (lenti - slow) applied to the clinical aspects of the infection. The old C-type viruses, which HIV resembles structurally, have been reclassified into two new groups, neither of which include complex retroviruses. There is some evidence that progression in SOME (but not all) Third World cohorts may be faster than in the developed world: as I hinted to in a prevous post, this may well be due to dual infection, with the second hit of HIV being enough to tip the balance between viral replication and immune control. I raised the point at a research lecture once and the investigator said that it was a real effect, but the mechanism wasn't yet known - my proposal was as good as any. There is plenty of anecdotal evidence to support the case, but no-one has (to my knowledge) done a prospective cohort study looking for dual infection preceding a more rapid immune decline - it would be very neat indeed to show that, but the work involved would be extensive and very long-winded. I have no doubt that other factors such as chronic malnutrition may also play a role in the speed of progression to AIDS in some people, but that doesn't detract from the underlying infection with HIV being the main problem.

I'm impressed that if _I_ cannot answer his questions then the entire HIV-AIDS hypothesis fails. I only wish I had such power! On the other hand, with power comes responsibility, so maybe not.

I only wish Mr Russel's case WOULD rest...

I should also point out that I'm not ignoring Mr Tylers comments and references regarding AZT oxidation: quite simply Dr Flegg replied on the important point and there wasn't a great deal I felt I could add to the AZT issue. The references he supplied were actually quite intriguing, and while they don't support AZT being "oxidative" they do add to the understanding of AZT-mediated mitochondrial toxicity (which then, subsequently, affects the redox state). I found the precis and evidence rather better presented that what the Perth Group usually churn out. I interpret the findings slightly differently, in that the AZT-mediated mitochondrial toxicity is linked to alterations in GSH, rather than a direct cause through a chemical redox reaction. I also would argue that AZT, in combination therapy, is effective virologically and clinically. It is effective in monotherapy for a number of months in vivo, and in tissue culture systems, but has no effect on survival. It is a bad drug, but it isn't even the worst anti-retroviral - the obsession with AZT among those questioning the HIV/AIDS paradigm is worse than that displayed with the Monagnier data. Most notably, the Swiss Cohort study Mr Tyler quotes from is also one of the strongest bits of evidence to support the clinical benefits of antiviral medication [9]. The side effects may be bad, but they are clearly preventing opportunistic infections and death - contrary to what some would have us believe. The effects of combination therapy from the mid 1990's should have been the death-knell for those questioning the HIV-AIDS paradigm, since they so clearly showed the benefits of attacking the virus. 10 years on, it appears not.

I am not "want[ing] to protect and propagate the 'HIV' paradigm at all costs " but I am wanting to prevent the spread of potentially dangerous misinformation and falsehood about a lethal infection. I have a character flaw in that I simply HAVE to correct someone if they're wrong... I hope that when I am corrected I will be as gracious as I expect others to be.

Nick Bennett

1. Goedert et al. Eur J Epidemiol. 1985 Sep;1(3):155-9. "Epidemiological evidence that HTLV-III is the AIDS agent."

2. Baskin, G.B., et al., Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta. Vet Pathol, 1988. 25(6): p. 456-67.

3. Chakrabarti, L.A., et al., Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection. J Virol, 2000. 74(3): p. 1209-23.

4. Koopman, G., et al., The relative resistance of HIV type 1- infected chimpanzees to AIDS correlates with the maintenance of follicular architecture and the absence of infiltration by CD8+ cytotoxic T lymphocytes. AIDS Res Hum Retroviruses, 1999. 15(4): p. 365-73.

5. Kaul et al. J Immunol. 2000 Feb 1;164(3):1602-11. "HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi."

6. Ho et al NEJM 1989 321:pp 1621-1625 "Quantitation of human immunodeficiency virus type 1 in the blood of infected persons."

7. Winter et al Sex Transm Inf 1999;75:26163 "Asymptomatic urethritis and detection of HIV-1 RNA in seminal plasma"

8. SI-MOHAMED et al JOURNAL OF CLINICAL MICROBIOLOGY p. 20552059 Vol. 39, No. 6 "Quantitation of Human Immunodeficiency Virus Type 1 (HIV- 1)RNA in Cell-Free Cervicovaginal Secretions: Comparison ofReverse Transcription-PCR Amplification (AMPLICORHIV-1 MONITOR 1.5) with Enhanced- SensitivityBranched-DNA Assay (Quantiplex 3.0)"

9. Egger et al. BMJ. 1997 Nov 8;315(7117):1194-9. "Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study."

Competing interests: None declared