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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 ask an important question to which there is no answer at this time. When clinical trials of TMC-125, a novel NNRTI with broad activity against most NNRTI-resistant strains, as a microbicide are conducted, we will learn if resistance occurs in the vagina and rectum, whether this compromises its effectiveness as a microbicide, and whether these resistance viruses lead to infection with the same NNRTI mutations.

Note that microbicides are potentially useful for both men and women, and for both vaginal and rectal sex.

A few other points may be useful. The likelihood of resistance may vary with the characteristics and class of drug being tested, which is one argument in favor of drugs with activity which differs from current ART. There are likely to be enormous differences in the concentration of drug in a microbicide as compared to blood, so a single class of drug, e.g. NNRTIs, may behave differently in a microbicide compared to its activity in plasma.


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