Re: Re: Reply to James Whitehead 8 January 2005
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Nicholas Bennett,
Infectious Disease Postdoc Clinician
Department of Pediatrics, University Hospital, Syracuse NY

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Re: Re: Re: Reply to James Whitehead

One line from Mr Whitehead's post stood out for me:

"HIV-1 encodes for one of the human glutathione peroxidases."

Which comes from the abstract of a referenced article. [1]

Unfortunately I don't have access to the fulltext, and this statement seems very much at odds with what I understand the genome of HIV to contain. As far as I am aware HIV contains 3 enzymes: protease, reverse transcriptase and integrase. The other genes encode proteins that are structural or perform roles that are due to protein-protein or protein-RNA interactions rather than catalysing a particular reaction.

In fact, glutathione peroxidase (GP) activity in AIDS patients is _lower_ than in uninfected controls (but higher than in HIV-infected but non-AIDS patients) [1, 2] and the logic that HIV therefore reduces GP levels makes no sense - at least through that mechanism! Virally-encoded homologues of human genes tend to result in the effects of over-expression (e.g. tumours, immune evasion).

My personal opinion is that the GSH/trace element deficits are secondary to the immune-dysfunction induced by HIV (chronic overstimulation, skewed cytokine environment) but then compound the problem. They may also be affected by the malabsorption syndromes common in HIV-infected people (caused directly by HIV, or CMV in the gut) - burning the candle at both ends. While I disagree with Foster's theory on the basis of the genetics of the virus, that's not to say that HIV doesn't do it in another way.

What is interesting, and which Mr Whitehead brings to our attention, is that by treating this apparent "symptom" of the disease the outcomes can improve. There is considerable evidence that treating HIV directly can have an effect, but it is not permanent and can have costly side- effects. Further measures are clearly needed - and whether these are cytokine stimulation to clear the proviral reservoir, an effective vaccine, or improved immune function through better supplementation doesn't really matter: so long as it works.

Nick Bennett njb35@cantab.net

1. Foster HD. Med Hypotheses. 2004;62(4):549-53. "How HIV-1 causes AIDS: implications for prevention and treatment. "

2. Dworkin et al. Biol Trace Elem Res. 1988 Jan-Apr;15:167-77. "Abnormalities of blood selenium and glutathione peroxidase activity in patients with acquired immunodeficiency syndrome and aids-related complex."

Competing interests: None declared