Loading...
For 20 years, researchers have been testing potential anti-HIV microbicides in humans, with no success. Now, the first of a new generation of antiretroviral-based microbicides has proven efficacious in a randomized, placebo-controlled trial conducted in both urban and rural South Africa.
A total of 889 sexually active, HIV-uninfected women (age range, 18–40) received either 1% tenofovir gel or placebo gel, with instructions to administer the gel intravaginally within 12 hours before sex and also within 12 hours after sex. Gel adherence was measured using returned applicators and was classified as either high (>80%), intermediate (50%–80%), or low (<50%). Mean follow-up was 18 months.
Overall, the study retention rate was 95%, and the average rate of gel adherence was 72%. In an intent-to-treat analysis, the incidence of HIV infection was 5.6 per 100 person-years in the tenofovir group versus 9.1 per 100 person-years in the placebo group, for an incidence rate ratio (IRR) of 0.61 (95% confidence interval [CI], 0.40–0.94; P=0.017). Efficacy correlated with gel adherence: Tenofovir reduced the incidence of HIV infection by 54% among women with high adherence, 38% among women with intermediate adherence, and 28% among women with low adherence. The tenofovir and placebo groups had similar rates of adverse events. Importantly, the women who became HIV-infected in the tenofovir group did not show evidence of tenofovir-related resistance mutations or thymidine analogue mutations.
Unpublished data presented at the 2010 International AIDS Conference (Abstract TUSS0502) showed that the tenofovir group also had a 51% reduction in the incidence of herpes simplex virus (HSV)-2 infection, apparently independent of the effect on HIV. The incidence of new HSV-2 infections was 9.9 per 100 person-years in the tenofovir group versus an alarming 20.2 per 100 person-years in the placebo group (IRR, 0.49; 95% CI, 0.30–0.78; P=0.003).
Abdool Karim Q et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010 Jul 19; [e-pub ahead of print]. (http://dx.doi.org/10.1126/science.1193748)
Comment
These solid data provide proof of concept that topical antiretrovirals can serve as effective anti-HIV microbicides. Given the efficacy and pharmacology of tenofovir in HIV treatment, and the positive animal studies leading up to this trial, the results should not necessarily be surprising, but they are most welcome. Additional trials are now needed to confirm these findings, including the reduced HSV-2 incidence. The ongoing VOICE trial, conducted by the NIH-funded Microbicide Trials Network, should provide additional efficacy data on tenofovir gel as well as oral tenofovir and oral tenofovir/FTC (Truvada) in the next 3 years. Other ongoing studies are now evaluating potentially more convenient or longer-acting modes of microbicide delivery, such as intravaginal rings, and additional antiretroviral classes. We are still far from having a microbicide available clinically, but at least, a female-controlled HIV prevention method finally looks possible.