Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir

Objective: To assess the effect of the antiviral drug acyclovir on the frequency of subclinical shedding of herpes simplex virus (HSV) in the genital tract. Design: A double-blind, placebo-controlled, crossover clinical trial. Setting: A university-based virology research clinic. Patients: 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. Intervention: Participants were randomly assigned to receive either acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period, and then placebo for 70 days, or the study medications in the reverse order. Measurements: Women collected daily genital swabs of the vulvar, cervicovaginal, and perianal areas for HSV culture, maintained a diary of genital lesions, and were examined at the time of recurrences. Results: In an intent-to-treat analysis of the initial treatment period, 15 of the 17 women who received placebo and 3 of the 17 women who received acyclovir had at least 1 day of subclinical shedding (P < 0.001). Among the participants who received placebo, subclinical shedding occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the participants who received acyclovir (P < 0.001). The relative risk for subclinical shedding was 0.09 (95% CI, 0.03 to 0.35) for the women who received acyclovir compared with the women who received placebo. In a paired analysis of 26 women who completed both arms of the study, acyclovir therapy was associated with a decrease in the frequency of subclinical shedding; subclinical shedding occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days with acyclovir (P < 0.001)-a 94% reduction. The frequency of subclinical shedding was reduced at all anatomic sites and in all patients. Conclusions: Daily therapy with oral acyclovir suppresses subclinical shedding of HSV-2 in the genital tract, suggesting that studies to evaluate the use of acyclovir in preventing HSV-2 transmission are warranted.