Perhaps the most welcome news at AIDS 2010 was a report by Salim Abdool Karim and fellow investigators with the CAPRISA 004 trial showing that a vaginal tenofovir gel offered women moderate protection against HIV infection during sex.
Prior microbicide studies in humans have not produced impressive results, but unlike earlier products, this gel is not just a physical barrier but contains an antiretroviral drug that actively inhibits HIV replication (marketed as Viread in its oral formulation).
As described at the conference and in the July 19, 2010, issue of Science, this Phase IIb trial included nearly 900 initially HIV negative women enrolled at two sites (one urban and one rural) in KwaZulu-Natal, South Africa. The women were sexually active, not pregnant, had no other sexually transmitted diseases and were considered to be at high risk for HIV infection. They were randomly assigned to apply either 1% tenofovir gel or an inactive placebo gel, inserted into the vagina using pre-filled applicators, within 12 hours before and 12 hours after having sex.
Women using tenofovir gel had an HIV incidence rate of 5.6 new infections per 100 person-years, compared with 9.1 for participants using placebo gel. Overall, women using the microbicide had a 39% lower risk of becoming infected. Risk reduction reached 54% among participants who achieved good adherence, but fell to 38% for those with intermediate adherence and 28% for those with only poor adherence. Tenofovir gel also halved the risk of herpes simplex virus type 2 infection (the cause of genital herpes).
Tenofovir gel was generally well-tolerated without notable toxicities, including no increase in serum creatinine, a marker of impaired kidney function. Almost all study participants found the gel to be acceptable and said they would use it if it were shown to prevent HIV infection.
Based on these findings, the CAPRISA researchers concluded, "Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use."
The study findings were widely heralded as the first demonstration that a microbicide can reduce HIV infection in humans under real-world conditions. But tenofovir gel is still in early development and is not expected to be available for at least a few years. With its safety and acceptability established, it will now move into larger Phase III efficacy trials.
The Microbicide Trials Network is currently conducting a related trial called VOICE, testing tenofovir gel applied daily rather than only at the time of sex. Advocates have also called for testing it as a rectal microbicide for anal sex. In early November, CONRAD, the agency spearheading the development of tenofovir gel, announced that the FDA has granted "fast track" status to enable faster review of studies.
"For the first time, we have seen results for a woman-initiated and -controlled HIV prevention option," said UNAIDS executive director Michel Sidibe. "If confirmed, a microbicide will be a powerful option for the prevention revolution and help us break the trajectory of the AIDS epidemic."
Liz Highleyman (firstname.lastname@example.org) is a freelance medical writer based in San Francisco.