Background: Having symptomatic herpes simplex virus type 2 (HSV-2) infection is thought to increase a patient's risk of contracting human immunodeficiency virus type 1 (HIV-1) infection. Several trials have shown that daily HSV-2 therapy can reduce plasma HIV-1 levels by 0.25 to 0.50 log10 copies per mL. Celum and colleagues conducted a randomized, double-blind, placebo-controlled trial to evaluate if suppression of HSV-2 infection might prevent transmission of HIV-1 infection.
The Study: The authors recruited 3,408 heterosexual couples with discordant HIV/HSV status (i.e., one partner was seropositive for HIV-1 and HSV-2, and the other partner was HIV-negative but could be positive or negative for HSV-2). Partners with HIV-1 infection were randomized to receive acyclovir (Zovirax), 400 mg twice daily, or a placebo, and both partners were monitored for two years for changes in health status and HIV transmission. The primary end point was a new diagnosis of HIV-1 in the previously negative partner. Exclusion criteria for partners with HIV-1 infection included pregnancy or persistent genital ulcers. These patients were also excluded if they were taking antiretroviral therapy, had a CD4 count of less than 250 cells per mm3 (250 × 109 per L), or had evidence of AIDS.
Results: Mean HIV-1 plasma concentration was significantly reduced by 0.25 log10 copies per mL in the acyclovir group compared with the placebo group, as was the risk of symptomatic genital ulcer disease (risk ratio = 0.39). However, HIV-1 transmission rates were equivalent between the groups. No differences in transmission rates were noted with respect to sex, partner's HIV-1 viral load or symptomatic genital ulcer disease, or to the level of adherence with the assigned treatment.
Conclusion: The authors conclude that daily acyclovir therapy is ineffective in preventing transmission of HIV-1 infecton from a partner who is HIV-1– and HSV-2–positive to the partner who is HIV-negative, even with reductions in HIV viral load.