Microbicides Are Back!
Abstract & Commentary
By Alison Edelman, MD, MPH, Associate Professor, Assistant Director of the Family Planning Fellowship, Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, is Associate Editor for OB/GYN Clinical Alert.
Dr. Edelman reports no financial relationship to this field of study.
Synopsis: The use of tenofovir gel in the vagina, a nucleotide reverse transcriptase inhibitor, reduced HIV acquisition in women.
Source: Karim QA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010 Jul 19; Epub ahead of press. Available at: www.sciencexpress.org.
The "Caprisa 004" trial was a randomized double-blind controlled trial of 1085 sexually active, HIV-negative, high-risk women in South Africa over 2.5 years (889 women were included in the final analysis). Women were randomized to a 1% tenofovir gel or placebo to be used before and after each act of intercourse. The main goal of the study was to assess the safety and effectiveness of the study gel in the prevention of HIV infection in women. Adherence to study medications was documented by the return of used gel applicators correlated with the number of coital episodes. All participants were given comprehensive counseling on HIV prevention strategies and reproductive health services. Overall, the use of tenofovir gel decreased HIV incidence by 39% and in "high" users (use of gel > 80%), by 54%. Even "low" users (use of gel < 50%) had a benefit over placebo, with a reduction in incidence of 28%. Gel acceptability was high (97%). Additionally, no tenofovir resistance was found in women that seroconverted. Rates of adverse events were similar between the two groups.
Commentary
The revelation in the early 2000s that nonoxynal-9 (N-9) did not prevent HIV and actually might enhance HIV transmission was devastating. Although N-9 has activity against HIV in laboratory studies, human studies demonstrated that N-9 may enhance HIV transmission, most likely due to its harsh effect on vaginal and rectal mucosa.1,2 N-9 was and still is available in over-the-counter products like condoms and spermicide, but is not recommended for the prevention of HIV infection.3
As the burden of HIV for women is disproportionately high in areas where the epidemic still is rapidly spreading like Africa,4 a female controlled method that is coitally related is ideal, and the search has been on to find an effective method. Unfortunately, multiple experimental agents have been researched with no result. The CAPRISA 004 or 1% tenofovir gel is the first agent to show a positive effect. Tenofovir is a nucleotide reverse transcriptase inhibitor that is used orally for HIV treatment; it has an excellent safety profile and a long half-life. The downside of tenofovir is that there are few safety data in pregnancy, but the small number of pregnancies that occurred during this study showed no ill effects. The study is limited by self-reported use of the study drug and also by the fact that the highest gel adherence and effect was in women with the lowest coital frequency; however, they found this group still had similar HIV incidence rates.
It's promising to finally have a "win" in the fight against HIV/AIDS and to have another tool to empower women. Further research will need to confirm these results, work on how to increase adherence, and possibly combine with a vaginal contraceptive method for dual protection.
References
- Van Damme L, et al. Effectiveness of COL-1492, a nonoxynal-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomised controlled trial. Lancet 2002;360:971-977.
- Phillips DM, et al. Lubricants containing N-9 may enhance rectal transmission of HIV and other STIs. Contraception 2004;70:107-110.
- Sexually Transmitted Diseases Treatment Guidelines, 2006. CDC MMWR 2006;55(RR11):1-94. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/rr5511a1.htm. Accessed Aug. 20, 2010.
- 2004 Report on the global AIDS epidemic: 4th global report. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2004:22-58.
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