The Caprissa 004 study of a tenofovir 1% gel will be presented at the IAS meeting in Vienna tomorrow.  The study demonstrates 39% protection against acquisition of HIV-1 infection among heterosexual women counseled to use the gel before and after sexual intercourse.  The result is statistically significant, representing the first evidence of efficacy of a vaginal microbicide.

Tenofovir 1% vaginal gel was also partially protective against the acquisition of HSV-2 infection, measured serologically at the beginning and end of the study.  Compounds related to tenofovir have high levels of activity against HSV-2, although tenofovir itself is active only at high concentrations.  Such very high concentrations may have been achieved in the vaginal mucosal after repeated topical administration.  Further analysis of the activity of tenofovir against HSV-2 will be triggered by this clinical finding.  

The information is an important proof of concept for chemoprophylaxis, although the level of efficacy observed was modest.  It appears that additional information will be needed to confirm that tenofovir 1% vaginal gels are effective. The MTN VOICE trial will provide additional information.

This finding is increasing interest in the results of the iPrEx trial, which evaluates daily oral coformulated FTC/TDF for prevention of HIV-1 acquisition in gay men, transgendered women, and other men who have sex with men (MSM).  People are interested in learning whether oral PrEP may protect MSM, whether daily dosing is feasible (in contrast to the coitally dependent dosing used in Caprissa 004), and whether daily oral dosing may inhibit acquisition of HSV-2 .  

The Caprissa 004 study results are not generalizeable to MSM because of differences in the mucosal surfaces that are exposed and the sensitivity of the rectal mucosa.   Still, the success of the Caprissa 004 study, albiet partial, is a proof of concept for chemoprophylaxis for sexual transmission of HIV-1.  The next steps will focus on what limited efficacy to 39 percent overall, which may reflect partial adherence, limited drug exposure associated with coitally dependent dosing, and or limited activity of the single agent.  Some of these limitations are being addressed in the iPrEx trial, which uses 2 active agents (FTC and TDF), oral dosing, and daily use.  

We all congratulate Salim Abdool Karim and Quaraisha Abdool Karim in conducting a successful trial of a novel approach to vaginal microbicides.