Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse, NY
Send response to journal:
In reply to James Whitehead:
I cannot explain what is meant by oxidative stressors, since this seems to be a phrase most often used by the Perth Group! It seems to me that such things are environmental exposures (such as your examples of specific drug use) and are therefore going to be relatively indiscriminate in affecting a cohort of similar people. In contrast long-term decline in CD4 T cells occurs only in those with HIV infection.
I do not claim that secondary factors don't play a role in the rate of progression to AIDS - this has been shown time and again in the literature, but equally the single consistent feature is HIV infection.
There really is no distinction between those under excess enviromental exposure and those with low levels of antioxidants - the natural process of living creates quite enough free-radicals and oxidizing molecules!
I do not deny that AZT affects the mitochondrial control of the redox state, but I find it ironic that if so it cannot possibly fit with the Perth Group's assertation that HIV is only induced under oxidative conditions, since AZT inhibits HIV replication [1, 2, 3, 4]. Most importantly it does so selectively to cellular toxicity.
High levels of oxidative stress will contribute to cell dysfunction, and maybe death, but such deaths with be indiscriminate rather than specific for a single cell lineage (CD4 T cells!). This is my main criticism for the "oxidative stress causes AIDS" argument - it fails to explain the "magic bullet" characteristic of the disease, whereas HIV infects the very cell line in decline.
And the link between wasting and AIDS is one of the clearest risk factors.
It is not that I am claiming that antioxidants have no role whatsoever, but I do seriously dispute their role, independant of HIV infection, to cause AIDS. Similarly I do not dispute that AZT is a toxic drug, but I do dispute the claims that it is non-specific and cannot be antiviral.
Nick Bennett firstname.lastname@example.org
1. Mitsuya et al Proc. Nati. Acad. Sci. USA Vol. 82, pp. 7096-7100, "3'-Azido-3'-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro"
2. Furman et al Proc. Nati. Acad. Sci. USA Vol. 83, pp. 8333-8337, "Phosphorylation of 3'-azido-3'-interaction of the 5'-triphosphate virus reverse transcriptase"
3. Nakashima et al ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 1986, p. 933-937 "Inhibition of Replication and Cytopathic Effect of Human T Cell Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus by 3'- Azido-3'-Deoxythymidine In Vitro"
4. Inoue et al ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 1989, p. 576-579 "In Vitro Bone Marrow Toxicity of Nucleoside Analogs Human Immunodeficiency Virus"
Competing interests: None declared