Clinical Newswire, July 21, 2010 (Vienna, Austria) - A gel preparation of tenofovir reduced HIV infection significantly in a South African trial, and is the first demonstration of an effective vaginal antiretroviral microbicide. The tenofovir gel lowered HIV transmission rates by 39%, with no drug-related adverse effects. The CAPRISA (Centre for the AIDS Programme of Research in South Africa) 004 trial results were presented by Dr Salim Abdul-Karim, of CAPRISA, Congella, South Africa, in a special session at AIDS 2010, Vienna, on 20th July.
Women aged 18-40, who were sexually active but not infected with HIV, were recruited to the randomized trial (N=889). The women received either a hydroyethylcellulose (HEC) gel containing 40mg tenofovir was given to (n=445) or an HEC placebo gel (n=444). The gels were supplied in pre-filled vaginal applicators. Participants were instructed to apply the gel up to 12 hours before sex and up to 12 hours afterwards, but more than two doses per 24-hour period were not recommended. Participants were tested for HIV and pregnancy every month for 30 months. Comprehensive HIV-prevention counselling was given.
The tenofovir gel arm had an HIV incidence rate of 5.6 per 100 woman-years (38 cases), compared to 9.1 per 100 woman-years in the placebo group (60 cases; P=0.017). Infection rates fell over time in the placebo group, from 11.2 to 9.1 per 100 woman-years, but remained constant at <6.0 per 100 woman-years in the tenofovir group. After adjustment for baseline variables, the hazard ratio for tenofovir treatment was 0.63 (95% CI 0.42-0.94, P=0.025). Women with using the tenofovir preparation with high adherence (>80%) had a 54% reduction in HIV acquisition (P=0.025) compared with the placebo arm. Those with intermediate (50-80%) or low (<50%) adherence showed decreases in infection of 38% and 28%, respectively.
No differences between groups in overall adverse event rates were seen. Adverse events were reported by 93.4% of participants, but only five women discontinued the trial. In the women who contracted HIV, no resistance mutations to tenofovir were detected. There was also no evidence suggesting that tenofovir gel masked HIV infection in these women.
The CAPRISA 004 results offer the first hope that women may be able to protect themselves from HIV infection even when unable to negotiate condom use or monogamy. The trial offers proof that an ARV-based vaginal gel can prevent HIV transmission safely and effectively. The CAPRISA 004 trial was supported by CAPRISA and USAID. Gilead Sciences provided the tenofovir used for the gel.
Abstract: TUSS0503
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