Carraguard Microbicide Fails to Prevent HIV Infection in South African Study

By Liz Highleyman

Over the course of the epidemic, women and their advocates have urgently sought woman-controlled methods of HIV prevention, given that many women are unable to refuse sex or demand that their partners use condoms.

Microbicides -- gels or other products inserted in the vagina prior to intercourse --have been widely studied, but results so far have mostly been disappointing, including the finding that Ushercell cellulose sulfate gel was actually associated with an elevated risk of infection.

The discouraging news continued in the December 6, 2008 issue of The Lancet, with a report that one of the most promising microbicide candidates, Carraguard, did not reduce the risk of HIV infection in South African women.

Stephanie Skoler-Karpoff and colleagues conducted a randomized, double-blind trial comparing Carraguard -- a carrageenan (seaweed) derived compound developed by the Population Council -- versus placebo gel without the active ingredient.

The large study included more than 6000 sexually active HIV negative women aged 16 years or older at 3 South African sites. Participants were randomly assigned to use Carraguard (n = 3103) or placebo (n = 3099) gel, which they were instructed to apply vaginally, along with using a condom, before each act of vaginal intercourse.

Participants were followed for up to 2 years, with visits every 3 months including tests for HIV and pregnancy, pelvic exams, risk reduction counseling, and treatment for curable sexually transmitted infections and symptomatic vaginal infections.

Results

• In an intent-to-treat analysis, the HIV incidence rate was 3.3 per 100 woman-years in the Carraguard group (134 new infections) compared with 3.8 per 100 woman-years in the placebo group (151 infections); not a significant difference.

• There was no significant difference in the distribution of time to HIV seroconversion in the 2 arms.

• Rates of self-reported gel use were high and similar in both arms, at about 96%.

• Reported rates of condom use during the last sex act were also similar in both groups, at 64%.

• Based on applicator testing, however, the researchers estimated that gel was used for only about 42% of sex acts in both arms.

• 23% of women in the intention-to-treat population experienced adverse events, which were distributed evenly between the 2 arms (713 with Carraguard, 707 with placebo).

• 2% of the women reported adverse events related to gel use, again similar in both arms (48 with Carraguard, 47 with placebo).

• Serious adverse events occurred in 2% of women in the Carraguard arm and 3% in the placebo group, only 1 of which was considered possibly related to gel use in the placebo group.

Based on these findings, the investigators concluded, "This study did not show Carraguard's efficacy in prevention of vaginal transmission of HIV."

"Carraguard is unlikely to have a meaningful protective effect as used by study participants," they added in their discussion. Given the low adherence rate actually obtained -- in contrast with the high reported adherence -- "even a highly efficacious coitally-dependent product will have insufficient effectiveness in real-life settings."

12/9/08

References

S Skoler-Karpoff, G Ramjee, K Ahmed, and others. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. The Lancet 372(9654): 1977-1987. December 6, 2008. (Abstract).

W Cates and P Feldblum. HIV prevention research: the ecstasy and the agony. The Lancet 372(9654): 1932-1933. December 6, 2008