A vaginal microbicide that incorporates an antiretroviral (ARV) drug normally used to treat people with HIV is safe for sexually active HIV-negative women to use every day over an extended period, suggest results of a clinical trial of tenofovir topical gel.
Moreover, most of the women who participated in the study conducted in India and the United States adhered to a regimen involving either daily or sex-dependent use of the gel, report researchers from the U.S. National Institutes of Health-funded Microbicide Trials Network (MTN) at Microbicides 2008, an international meeting taking place Feb. 24-26 at the Hotel Ashok in New Delhi.
The findings, presented today for the first time, are a significant boost to HIV prevention efforts focused on the potential of "next-generation" microbicides to curb infection rates in women. Globally, nearly half of those living with HIV/AIDS are women, and between 70 and 90 percent of all HIV infections in women are due to heterosexual intercourse. In India and many other parts of the world, even married women and women with steady partners are at risk.
In this Phase II study, called HPTN 059, researchers wanted to understand if tenofovir was safe to use every day for six months compared to its use prior to each act of sex, and if women were able to adhere, or follow, each regimen. Researchers found both approaches equally safe and women's adherence to product use similar. Interestingly, most participants also said they would be willing to apply gel, including daily, if one were found effective to prevent against getting HIV from their sexual partners.
Microbicides are products designed to prevent the sexual transmission of HIV when applied topically on the inside of the vagina or rectum. Tenofovir gel is among a newer class of candidate microbicides that differ from early types because they have specific action against HIV. In addition, because tenofovir gel and similar products are longer acting, their use may not be required before each act of sex, which is not always practical or desirable for some women.
“Finding that daily use is both safe and feasible is important because we believe a daily approach may provide more sustainable protection against the virus in women who can't always predict when they will have sex. Based on what we have learned we can proceed with greater confidence on a path that will answer whether tenofovir gel and other gels with HIV-specific compounds will be able to prevent sexual transmission of HIV in women when other approaches have failed to do so. It is a critical time for all of us engaged in HIV prevention, and I truly believe we are turning a corner,” said Sharon L. Hillier, Ph.D., professor and vice chair for faculty affairs, and director of reproductive infectious disease research in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, who is MTN principal investigator and led the study.
According to UNAIDS, women represent nearly half, or 46 percent, of the 33.2 million people living with HIV/AIDS worldwide, and they are more than twice as likely as men to acquire HIV through sexual intercourse, due to both biological and cultural factors. Although correct and consistent use of male condoms has been shown to prevent HIV infection, women often cannot successfully negotiate condom use with their male partners.
HPTN 059 involved 200 sexually active HIV-negative women: 52 were enrolled at the University of Alabama at Birmingham (UAB) in Birmingham, Alabama; 48 at Bronx-Lebanon Hospital Center, Bronx, New York; and 100 women entered the study at the National AIDS Research Institute in Pune, India. The mean age was 32 and 64 percent of the women were married. All but one of the women at the Indian site were married compared to 28 percent of the women at the two U.S. sites.
Once enrolled, women were randomly assigned to one of four groups: tenofovir gel applied daily; tenofovir gel applied up to two hours before sex; placebo gel (without an active drug) used every day; or placebo gel applied prior to sex. Because the tenofovir and placebo gels look the same, neither researchers nor participants knew who had been assigned to use which gel during the six-month study period. Women were assessed at one month, three months and six months. Throughout the study, participants received free condoms and HIV risk-reduction counseling as well as routine testing and treatment for sexually transmitted infections.
The study found no differences in liver, blood and kidney function between the groups of women using either regimen of tenofovir gel and the groups assigned to use placebo, nor were there differences in these safety measures between groups using daily gel and groups using gel with sex. Likewise, researchers report no statistical differences in the development of genital symptoms such as itching and burning, which are considered minor. One woman became pregnant and stopped gel use. No participants acquired HIV during the study.
Adherence to treatment was also similar. According to structured interviews, 80 percent of the women instructed to use gel within two hours of having sex said they complied with the regimen. Of the women in the daily-use groups, an average of 83 percent reported study gel use in the past week. The two most cited reasons women gave for not using gel was menstruation (41 percent) and forgetting (23 percent).
Overall, 41 percent of the women indicated there was nothing they disliked about using the gel and 39 percent said it was easy to use. Other attributes of the gel women identified included its potential for protecting against HIV (19 percent), its smell and appearance (14 percent) and that it made sex more pleasurable (12 percent). Thirty-two percent didn't like that the gel was messy, but none of the women said sex was made less pleasurable because of the gel.
Importantly, when asked if they would use the gel if it were found to help prevent people from getting HIV, 90 percent of the women who had been assigned to use the gel at the time of sex and 96 percent of the women who had been asked to use gel daily said yes.
“Women are definitely willing to use a gel to protect against sexual transmission of HIV. That's very encouraging,” Dr. Hillier commented.