After two decades of research, investigators may have developed a microbicide that provides substantial protection against HIV.1 In a randomized trial of tenofovir, the first antiretroviral drug to be formulated as a microbicidal gel, the incidence of HIV infection was lower among sexually active South African women who used the microbicide than among those who used a placebo gel (5.6 vs. 9.1 cases per 100 woman-years). Use of tenofovir gel reduced HIV acquisition by 39% overall, and by 54% among women who used the gel correctly during more than 80% of their sex acts.
The researchers conducted the double-blind, placebo-controlled trial from May 2007 to March 2010. Some 889 women were recruited from two clinics in KwaZulu-Natal, South Africa: one in a rural area with an HIV incidence rate of 11% and the other in an urban area with an incidence rate of 16%. Women were eligible for the study if they were HIV-negative, aged 18–40, not pregnant and using a nonbarrier contraceptive method; had had vaginal sex at least twice in the 30 days prior to screening; and met several other criteria related to health and logistics. At enrollment and monthly follow-up visits, women received comprehensive HIV prevention services, including counseling, condoms and STI treatment.
Participants were instructed to insert one dose of their assigned gel (tenofovir or placebo) vaginally up to 12 hours before sex and another as soon as possible after sex, and to use no more than two doses in 24 hours. Correct and consistent use was encouraged during follow-up visits. During these visits, participants reported the number of times they had had vaginal sex and returned their used and unused gel applicators; the researchers classified the 5% of applicators that were not returned as unused. Participants were tested for HIV and pregnancy each month and were asked about possible adverse effects of the gel. The trial lasted 30 months.
On average, urban participants were slightly older than rural participants (25 vs. 23 years) and had had a greater number of lifetime sex partners (6.0 vs. 2.1). Fewer than 10% of women in either group were married, but most (93% of urban and 77% of rural women) reported having a stable partner. At baseline, the proportion of urban women who reported always using a condom during sex was nearly twice that of rural women (43% vs. 23%). About 80% of participants relied on injectable contraceptives.
During the trial, on average, participants returned 6.0 used applicators and reported 5.0 vaginal sex acts per month. A total of 884 women had had any sexual activity, and 72% of their sex acts were covered by the recommended two doses of gel. Among women who remained HIV-negative, the proportion of sex acts for which women used the gel as instructed increased from 55% during the first six months to 75% during months 18–24. Participants reported using condoms during 80% of sex acts, and the proportion increased slightly over the duration of the study. Nearly all women found the gel to be acceptable (97%) and reported that they would use it if it prevented HIV (98%).
Coital frequency declined over the course of the study, from 7.2 sex acts per month in the first six months to 3.1 per month in months 18–24. Women who reported high adherence to the tenofovir gel regimen reported lower-than-average coital frequency (3.2 sex acts per month vs. 6.7 among those with low adherence). However, coital frequency, condom use and adherence to the gel regimen did not differ between the tenofovir and placebo groups.
HIV seroconversion occurred among 38 tenofovir users and 60 placebo users. After six months of follow-up, the cumulative HIV incidence rate was 47% lower in the tenofovir group than in the placebo group (6.0 vs. 11.2 cases per 100 woman-years); the rate was 50% lower after 12 months (5.2 vs. 10.5 per 100 woman-years) and 39% lower after 30 months (5.6 vs. 9.1 per 100 woman-years). Tenofovir reduced the incidence of HIV to an even greater extent (54%) among the women who adhered best to the gel regimen—those who had used two doses of the tenofovir gel during more than 80% of their sex acts.
The researchers conclude that although corroborating evidence is needed, tenofovir gel appears to be a safe and effective method of preventing sexually transmitted HIV and that its benefits can be observed soon after initiation. They point out that the highest adherence to the gel regimen—and the highest level of effectiveness—was achieved among women with the lowest coital frequency, suggesting that the gel may have the "potential to alter the course of the HIV epidemic in southern Africa" by protecting women who have "infrequent but very high-risk sex with migrant men." Thus, the researchers posit, "this antiretroviral microbicide could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use."—H. Ball
1. Abdool Karim Q et al., Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women, Science, 2010, doi:10.1126/science.1193748, accessed Aug. 2, 2010.