Across many observational studies, herpes simplex virus type-2 (HSV-2) infection, is associated with a 2-fold to 3-fold increased risk for HIV-1 infection. Connie Celum, MD, University of Washington, Seattle, Washington, and colleagues investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 infection.

The researchers performed a randomised, placebo-controlled phase 3 trial in HIV-negative, HSV-2-positive women in Africa and men who have sex with men (MSM) from sites in Peru and the United States. Participants received either aciclovir 400 mg or placebo for 12 to18 months. Participants were seen monthly for dispensation of the study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling. Participants were seen every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 infection and the secondary outcome was incidence of HSV-2 genital ulcers.

A total of 3,172 participants were included in the analysis. The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group and 3.3 per 100 person-years in the placebo group. Incidence of genital ulcers was reduced by 47% in the aciclovir group, and incidence of genital ulcers confirmed to be due to HSV-2 was reduced by 63% in the aciclovir group. No serious adverse events were recorded in relation to aciclovir.

The authors concluded, "Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1." They added that additional studies will be needed to determine whether the lack of efficacy of aciclovir in reducing HIV acquisition and less than expected efficacy in reducing genital ulcers is due to drug absorption and metabolism, clinical response of genital ulcers to aciclovir, or persistent genital immune response after HSV-2 reactivation.

SOURCE: The Lancet

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