|A few questions......
May 2, 2009
Some time ago, I posted a question on sustiva (see returning to sustiva) and you promptly gave me an excellent reply concerning the liklihood of developing Sustiva resistance(K103N)following my overdose attempt. The part I forgot to ask, was if the NRTI's that I overdosed on would result in nuke mutations (M184V in particular) as I took a weeks supply of combivir and tenofovir. Just to recap, I had viremia at the time of the overdose, and was previously treatment naive. Good news, I am still undetectable on my current combo. Finally, what are your views on the recent discovery that HIV appears to be transfered cell to cell rather than as a free floating agent. Is this finding going to cast doubt on emerging therapeutic approaches such as CCR5 / Fusion inhibitors, monoclonal antibodies, etc, that inhibit direct HIV entry? Thanks again for the brilliant work you do. M
Response from Dr. McGowan
Thanks for your post, I am glad you have maintained an undetectable viral load back on treatment.
The drug(s) that are most vulnerable when treatment is stopped are those that are cleared most slowly from the n blood, which would be the NNRTI (Sustiva). The drug must be present in the blood for it to select resistant virus from the mixture of virus in the body.
Spread of HIV from cell to cell (called syncytia formation) has been observed in the laboratory in cultures of T cells outside the body (in vitro) for many years. The extent that T cell fusion occurs inside the body (in vivo) is not clear. The process of cell fusion occurs through viral interaction with co-receptors on the T cell surface (CCR5 or CXCR4) and through proteins produced by the virus (gp41). HIV that uses the CXCR4 coreceptor are the ones that form syncytia so the CCR5 antagonists would be unlikely to work, fortunatley only about half of people with HIV have CXCR4 using virus (even less early after infection). Fuzeon, the fusion inhibitor, may have some activity to stop the fusion process since it binds to gp41 and is being studied to see if it can be of any benefit to keep people healthy. Since our current medications: NRTIs, PIs, integrase inhibitors and protease inhibitors block the virus' ability to copy itself and make the components necessary for cell fusion (such as the gp41), shutting down the virus with effective combinations of these medicines would also block the virus' ability to induce syncytia. In other words, you do not have to add anything to your current medications.
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