the Prevention of HIV Infection in Women

Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

The CAPRISA 004 trial assessed effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445) with placebo gel (n = 444) in sexually active, HIV uninfected 18 to 40 year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behaviour and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years, i.e. person time of study observation, (38/680.6 women-years) compared to 9.1 per 100 women-years (60/660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence <>Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconvertors. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

Following 20 years of research, including 11 effectiveness trials of 6 microbicide candidates that did not protect women from HIV, this groundbreaking study has responded to Zena Stein’s 1990 call for a women-controlled method for HIV prevention (Am J Pub Health 80, 460-462). The vaginal gel was inserted anytime in the 12 hours before anticipated sex and once in the 12 hours after sex. This dosing strategy was inspired by the effectiveness of antiretroviral prophylaxis at the time of exposure for preventing mother-to-child transmission. Whatever way the data are analysed, the results show effectiveness. Women who used the gel more consistently had more protection. WHO and UNAIDS are convening a meeting at the end of August 2010 at the invitation of the South African government to consider what further research is needed, what would be the regulatory pathway for tenofovir gel, and what programmatic issues would need to be addressed. An example of the latter would be the optimal frequency of HIV testing - having a test every month, as was done in the trial, would not be practical. When the results were presented in Vienna at IAS 2010 there was a standing ovation – an extremely rare event in science. You can download the slides and watch the presentation