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Treating HIV in all body compartments
Nov 27, 2005

Hello doctors. Just wondering what your thoughts are about choosing a regimen that is effective in all body compartments. Does such a regimen exist? Can you please provide a list of potential drug combinations that would do this. I have done a lot of research but I am very confused with all the contradictory evidence provided. Also, I could not find any information on the effectiveness of FTC or Tenofovir in crossing the blood/brain or seminal barriers. Is FTC also similar to 3TC in this respect? Reccomendations are now favouring boosted PI's as part of a first line regimen but they are known to not cross the blood/brain or seminal barriers as well as NNRTI's due to protein binding. So do I choose an NNRTI or boosted PI? Pill counts and side effects are a concern but I can put up with this if the regimen works well. I think I would adhere poorly if there were major food restrictions though. I also have concerns about adding 2nd generation nukes to a first line regimen (ie abacavir and Tenofovir). Should I save these for later or use them now. I like the idea that Tenofovir is active in a greater number of cell types and is less toxic and that Abacavir is very effective in the brain and seminal fluid. Please help. I am a young 27yo Aussie guy who has been infected < 3 months who wants to take advantage of early treatment that will target HIV in all compartments and be very durable.

Response from Dr. Wohl

I very much applaud your enthusiasm and the amount of research you have done. As you state, there are theoretical advantages to regimens that can target HIV in different areas of the body where HIV can reside. Although trying to hit the virus in these compartments in a drive to prevent them from acting as a reservoir for HIV, there is not much evidence to indicate that a combo that includes drugs that can get into the semen and the CSF does better clinically than a regimen that does not achieve relatively good levels in these fluids.

For instance, no combo has beaten Sustiva+3/FTC+another NRTI - this despite the surprisingly poor penetration of Sustiva in to the CSF. The same could be said of Kaletra+3/FTC+another NRTI.

Further, as you mentioned, levels measures in fluid does not necessarily indicate what is happening at the level of the cell, where drug and its active metabolites can be concentrated.

Additionally, while compartments such as the genital tract and central nervous system may be important sanctuaries for HIV, resting cells that harbor virus are arguably the most important compartment that current antiretrovirals leave basically untouched.

So, in your case, I would suggest that rather than trying to concoct a brew of meds that try to reach everywhere, you stick with a regimen that is easy to take and proven to be potent.

Anticipating your disappointment with this response, I can report that in just looking at the CSF level compared to blood plasma, of the NRTIs AZT, d4T and abacavir achieve the highest levels. 3TC and FTC seem about the same. Tenofovir like the other NRTIs not listed above does not get into the CSF very well. Among the NRTIs it is Viramune (despite the CNS issues with Sustiva levels of the drug are not high in the CSF) that gets the highest levels. Of PIs, most reach very low levels except for indinavir. There are limited data on T-20 (fuzeon) but this agent may be very active in the lymph nodes.

DW



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