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CAPRISA 004 trial results may provide hope for anti-HIV microbicide gels
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A tenofovir-based microbicide gel may have reduced the incidence of new HIV infection by nearly 40% and cut herpes incidence in half in a cohort of women in South Africa, according to results presented at the 18th International AIDS Conference.
The study was conducted by the Center for the AIDS Program of Research in South Africa (CAPRISA) group, and the results were presented by Salim Abdool Karim, PhD, and his wife, Quarraisha Abdool Karim, PhD, both of CAPRISA.
Eligible women were aged 18 to 40 years, sexually active, did not have HIV and lived in KwaZulu-Natal, South Africa. There were 445 women randomly assigned to receive the study drug and 444 women assigned to placebo.
In the double blind trial, dubbed CAPRISA 004, women were instructed to apply the gel or placebo within 12 hours of sexual activity and a second dose as soon as possible and within 12 hours after sexual activity. The researchers observed results for monthly pregnancy tests, quarterly pelvic exams and blood samples taken at months 3, 12, 24 and study exit at 30 months.
Prevention of HIV, herpes
Among women with HIV, samples were obtained as close to the estimated date of infection (median 15 days, range 14-121 days) as possible and within 5 days of gel use (range, 3-8 days). Among women who did not become infected, samples were taken from a high-gel use visit and an exit visit. Samples for a high-gel use visit were obtained 3 days (range, 2-6 days) later and 5 days (range, 3-8 days) later for an exit visit.
Results indicated that HIV incidence was 5.6 per 100 women-years (38 infections in 680.6 women years) in the tenofovir arm and 9.1 per 100 women-years (60 infections in 660.7 women-years) in the placebo arm (incidence rate ratio, 0.61; P=.017).
Among women who reported using the gel 80% of the time or more, HIV incidence was 54% lower in the tenofovir group (P=.025). Also in the tenofovir group, intermediate adherers, defined as women with 50% to 80% adherence rates, were 38% less likely to acquire HIV, and low adherers, defined as women with less than 50% adherence, were 28% less likely to become infected. Overall, tenofovir use reduced incidence of new HIV infection by 39%.
In presenting the results with HIV, the researchers also noted that the gels were 51% effective in preventing genital herpes infections in the women participating in the trial.
“Tenofovir gel has a potential dual effect in preventing HIV,” Salim Abdool Karim said in a press release. “Since women with genital herpes are much more likely to become infected with HIV, the additional protection of tenofovir gel against herpes creates a second mechanism, whereby the gel may have a bigger impact in preventing HIV. The trial results are a significant first step toward establishing the effectiveness of antiretroviral drugs for HIV and genital herpes prevention; confirmatory studies are now urgently needed.”
Presence of tenofovir
The CAPRISA 004 trial also assessed whether the tenofovir gel was associated with HIV seroconversion. The researchers compared tenofovir and tenofovir diphosphate exposure in the blood, genital tract secretions and genital and cervical tissue of 50 seroconverters with 40 non-seroconverters who reported frequent sexual activity and gel use.
Tenofovir was present in the genital tract samples of 36% of women with HIV and 83% of women who were not infected. The drug was present in the blood of 9% of infected women and 30% of uninfected women.
Tissue biopsy results indicated that 24 days (range, 18-48 days) after last reported gel use among HIV-positive women, 20% of vaginal and 13% of cervical tissues contained tenofovir. Tenofovir diphosphate was present in 16% of vaginal and 7% of cervical tissues from the same samples.
Broader effect
The researchers also created a statistical model calculating the potential effect of a comprehensive rollout of tenofovir microbicide gel. The researchers assumed a range of coverage from 50% to 80% and a 40% to 50% efficacy rate in preventing transmissions.
Results indicated that 40% efficacy with 50% coverage could prevent as many as 271,000 infections, and 50% efficacy with 80% coverage could prevent up to 602,000 new HIV infections in 10 years. The researchers noted that there were no adverse events considered to be related to the study drug. – by Rob Volansky
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All presented at the International AIDS conference; July 18-23, 2010; Vienna, Austria.