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NNRTI microbicide: TMC-120
Apr 26, 2004

Recently, J& J gave the IPM the right to develop TMC-120 (by subsidiary Tibotec) as a topical microbicide. My question relates to the use of such molecules as microbicides and the possibility of resisitance developing to members of this class of compounds. Do you believe these types of molecules may impart resistance should women with HIV use such a product repeatedly? I appreciate your thoughts.

Response from Dr. Sherer

You have raised an important question for which there is no answer at the present time. We will only know the answer to your question in regard to TMC-120 when clinical trials are conducted, and vaginal and blood samples are analyzed for the presence of resistance mutations.

It may be useful to make a few points in anticipation of these results. First, it is quite possible that the answer to the above question will differ, depending on the characteristics and class of the drug being tested. TMC-125 is an NNRTI, which are known for susceptibility to single point mutations, but it has excellent activity against most known NNRTI-reistant viruses, so it is not yet clear if it shares that weakness. Secondly, it is also possible that the implications of the development of resistance in organisms in the vagina and cervix will differ from the implicationso of resistance mutations in circulating blood, i.e. the type we identify with standard resistance tests. This relates to the different purpose of microbicides, which is to prevent infection by inhibiting viral replication before viral entry occurs.

And finally, and most importantly, it remains to be seen whether the development of resistance mutations in virions in the vagina, cervix, or rectum results in acquisition of virus carrying those mutations. While intuitively it makes sense that this would occur, it remains to be demonstrated that it does happen, and, as noted above, the likelihood and the frequency at which it occurs may vary with different agents.

subtype E survival time
NNRTI microbicide: TMC-120

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