Re: Re: Re: HIV Tunnel Vision 21 July 2004
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Nicholas Bennett,
Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY

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Re: Re: Re: Re: HIV Tunnel Vision

I apologise to James Whitehead if it appeared as if I was criticising his recent post: my comment on "those proposing oxidative stress as an entire replacement..." was indeed directed at those with far stronger views such as the Perth Group. I also apologise because my specialist field is far more viral than immunological or dietary, and most of the commments I can make on oxidative stress affecting the immune system are by necessity opinion rather than factual!

With that caveat, I shall try to address his questions:

Coming from the awareness that HIV induces long-term chronic immune system ACTIVATION (yes, it is the activation that is pivotal to much of the decline in CD4 cells: they are replicating and therefore dying through regulatory apoptosis but are not being replaced by the thymus) I can well imagine that HIV would cause a release of activating cytokines and immunomodulatory molecules. Some of these might be "oxidative", in terms of Nitric Oxide release for example, but I honestly cannot say for sure.

I did read with interest though some of the references posted here which linked oxidative-type immune messengers activating NF-Kappa-B, which is the primary transcription factor of HIV. Since HIV infection leads to immune activation, which leads to further HIV infection (preferentialy of activated T cells, rather than quiescent memory or naive T cells) which leads to further activation...this kind of feedback loop would be entirely consistent. It is likely, in my opinion, that if oxidative immune signals are involved in the activation of NF-kB then they almost certainly are involved in HIV infection. But that's only an opinion, and I would still say that the original stimulation (eg HIV) has to exist in order for the loop to kick off. Certainly shutting down HIV replication seems to shut down the inappropriate immune activation.

I don't know if oxidative "stress" per se plays a role in any of the mechanisms given, but oxidative messenger signals might. It does certainly seem as if cheap antioxidant vitamins do affect progression to AIDS, but whether this proven clinical benefit is due to a reduction is the aforementioned immune messengers I cannot say. I'm not aware of the mechanism being investigated.

I don't know if poor nutrition itself (as opposed to specific losses in other vitamins) directly speeds up progression or risk of certain specific diseases. Obviously though, serious malnutrition can cause a clinically increased risk of minor opportunistic infections and poor healing, and good nutrition should be a part of every therapeutic target. I can see an argument for, in particularly poor countries, diverting funds away from antiviral medications towards simple measures like better sanitation, education and food. Such is the evil of rationing.

This is entirely seperate from the issue of vertical transmission of the virus, which can be relatively safely and cheaply prevented using antivirals at the time of birth. I don't believe any intervention other than Caesarian section has shown anywhere near as good a benefit.

I apologise for the lack of references, but most are mentioned here in the Rapid Responses and are in the PubMed archives (or alternatively try the Google Groups advanced search feature looking in misc.health.aids). I'm also at the disadvantage of commenting outside my field!

I hope that's helpful in some way, regardless.

Competing interests: None declared