Acyclovir to Prevent HIV Infection?

In the absence of an effective vaccine to prevent HIV infection, alternative strategies to diminish infection rates are desperately needed, particularly in Africa. One possible avenue involves suppressing herpes simplex virus (HSV) infection, which is thought to contribute to a substantial proportion of HIV infections in sub-Saharan Africa. In a previous trial of coinfected women in Burkina Faso, suppressing HSV infection reduced HIV viral load in blood and genital secretions (Journal Watch Infectious Diseases Feb 21 2007). Whether such suppression might reduce the incidence of HIV infection in HSV-monoinfected women remains unknown. Researchers have postulated that HSV recurrences might facilitate HIV infection by disrupting epithelial barriers to infection and by creating a permissive environment of CD4 cells within HSV genital ulcers.

At the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Watson-Jones and colleagues described a randomized, double-blind trial that was conducted among 821 HIV-negative Tanzanian women who had serologic evidence of HSV-2 infection and were at relatively high risk for HIV infection because of their work in bars, guesthouses, and similar venues [Abstract MOAC104]. Participants received twice-daily oral acyclovir (400 mg) or placebo for up to 30 months and were followed at 3-month intervals.

In an intent-to-treat (ITT) analysis, acyclovir had no demonstrable effect on the incidence of HIV infection (4.25% with placebo and 4.29% with acyclovir). Similar null results were seen in a modified ITT analysis, in which results were censored for the 216 women who withdrew from the study (mostly because of pregnancy). Although acyclovir seemed to have some modest benefit in the ITT analysis among women who were most adherent, the finding was not statistically significant.

These disappointing results may be at least partially attributable to poor adherence. During the first 6 months of the study, only about 80% of women took at least three quarters of the tablets prescribed, and adherence declined with longer follow-up. Although acyclovir therapy remains a potentially valuable strategy for reducing HIV acquisition among HSV-infected women, the practical issues surrounding this strategy must be addressed before its ultimate role can be determined.