Trials Planned to Confirm Efficacy of Tenofovir Microbicide Gel

Following the encouraging results from the recent Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial that demonstrated that vaginal application of a microbicide gel containing 1% of the antiretroviral tenofovir, which is used in the treatment of HIV, reduced the HIV incidence in 889 South African women by 39%, researchers are planning two confirmatory trials that could potentially lead to licensure of the microbicide candidate (see VAX September 2010 Spotlight article, Microbicides Finally Gel, Securing Spotlight in Vienna).

Researchers now hope to be able to replicate the results of CAPRISA 004 in a confirmatory trial involving 3,000 women enrolled at six clinical research centers in South Africa. The trial known as FACTS 001 will evaluate the same dosing regimen tested in the CAPRISA 004 trial, pending approval by South African regulatory authorities. Women in CAPRISA 004 received regular HIV prevention counseling and were instructed to apply the gel up to 12 hours before sex and as soon as possible following sex, but within 12 hours, a regimen referred to as BAT24. Eligibility criteria for enrollment in the FACTS 001 trial will be expanded to include girls ages 16 and 17 because they are considered to be at high risk of HIV infection through heterosexual sex. Salim Abdool Karim, director of CAPRISA, says he hopes to begin the confirmatory trial in early 2011, with results expected in 2013.

A second confirmatory trial is also being planned to determine whether a single dose of the microbicide gel around the time of intercourse is sufficient to protect against HIV. A trial referred to as MDP 302 will compare the efficacy of the CAPRISA 004 BAT24 dosing regimen with one dose of tenofovir gel right before sexual intercourse or, failing that, as soon as possible after intercourse. Plans are to enroll 3,750 women from up to five African countries, including Uganda, Tanzania, and Mozambique.

The South African Department of Science and Technology and the US Agency for International Development (USAID), which together funded CAPRISA 004, will provide most of the funding for FACTS 001. The MDP 302 trial will be partly funded by the Medical Research Council in the UK, with other funding sources to be determined.

Other follow-up studies will determine the best way to deliver the microbicide and how tenofovir gel use impacts the safety and effectiveness of oral tenofovir for HIV treatment. —Regina McEnery