Leaders from around the world in AIDS research and health policy gathered in Toronto in August 2006 for the XVI International AIDS Conference. A key theme of the conference was HIV prevention, including assessment of old standards as well as new strategies. Leigh Peterson of Family Health International presented preliminary data from a current AIDS prevention study of women in Ghana (2006). This new prevention strategy is called pre-exposure chemoprophylaxis, or PrEP. In the PrEP strategy, HIV-negative individuals with high risk behavior take a single daily dose of tenofovir, a widely prescribed anti-retroviral. Tenofovir is a nucleotide reverse transcriptase inhibitor, meaning tenofovir’s unique shape blocks the reverse transcriptase protein in HIV from making new copies of the virus. The FDA approved tenofovir in 2001 and was a good drug candidate for this study because it has few side effects and showed low levels of resistance. The idea of prophylaxis is not new. It is most commonly used to prevent malaria; but it has not been tested as a valid strategy for preventing HIV until now.
According to the Family Health International study, 936 HIV-negative women in Ghana, Cameroon, and Nigeria were enrolled into a double-blind, 1:1 randomized trial. Half of the women received a daily 300 mg dose of tenofovir and the other half received a placebo. Between June 2004 and March 2005, participants were evaluated monthly for adverse events, abnormal serum creatinine and phosphorus levels, were HIV tested, and were re-supplied with drugs. Before the study was completed, the Nigerian trial was stopped due to faulty laboratory monitoring; and the Cameroon site prematurely closed due to ethical concerns about the study. The preliminary results presented at the AIDS conference showed that only two out of 363 women in the tenofovir group contracted HIV compared with six out of 368 in the placebo control group. While those in the PrEP group were 65% less likely to become infected, the difference was not statistically significant due to a small population size. There were no significant differences in adverse events or laboratory abnormalities between the two groups. Gilead, the maker of tenofovir, has committed to making the drug available at no profit cost to the areas where the need for prevention is greatest (Kresge 2003).
The Centers for Disease Control and Prevention is currently sponsoring three clinical trials of PrEP in homosexual men in San Francisco and Atlanta, men and women in Botswana, and intravenous drug users in Thailand (2006). These trials divide each subpopulation into two experimental groups: one taking tenofovir and the other taking truvada, a combination of tenofovir and emtricitabine. The results from these trials will not be available for at least another year.
Both of these PrEP trials attempt to answer the same questions: will prophylaxis reduce the risk of HIV transmission, is tenofovir a safe drug for uninfected individuals to take daily, and how will PrEP affect HIV risk behavior? PrEP is intended to be a part of an integrated approach to HIV prevention and should be used in concert with condoms, AIDS education and counseling, rather than by itself. If the PrEP strategy proves to be effective, then it could result in millions of averted AIDS deaths globally. One reason PrEP studies target women in Africa is because they are currently the most vulnerable and unprotected victims of AIDS. Specifically, PrEP would offer protection for women who are unable to negotiate condom use during sex and represents a big step toward empowerment of women in the third world. Important obstacles under consideration with PrEP are: the development of tenofovir-resistant HIV, increased risk behavior of people taking PrEP, and the cost effectiveness of using medication as a prevention strategy. Nonetheless, the discussion of an HIV prophylaxis at the international AIDS conference represents an expansion of HIV prevention strategies and the potential to avert future AIDS deaths.
Thanks for listening, I’m Wes Fiser
Centers for Disease Control and Prevention. CDC Trials of Pre-Exposure Prophylaxis for HIV Prevention: Clinical Trials in Botswana, Thailand, and the United States. August 2006.
Kresge, Kristen. Tenofovir as Pre-Exposure Prophylaxis. American Foundation for AIDS Research. February 2003.
Peterson, L et al. Findings from a double-blind, randomized, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) for prevention of HIV infection in women. XVI International AIDS Conference, Toronto. August 13-18, 2006. Abstract THLB0103.