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.