Objective: To assess the effect of the antiviral drug acyclovir on the
frequency of subclinical shedding of herpes simplex virus (HSV) in th
e 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 o
nly and genital herpes of less than 2 years' duration. Intervention: P
articipants were randomly assigned to receive either acyclovir, 400 mg
twice daily for 70 days, followed by a 14-day washout period, and the
n placebo for 70 days, or the study medications in the reverse order.
Measurements: Women collected daily genital swabs of the vulvar, cervi
covaginal, and perianal areas for HSV culture, maintained a diary of g
enital 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). Amon
g the participants who received placebo, subclinical shedding occurred
on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among th
e participants who received acyclovir (P < 0.001). The relative risk f
or 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. I
n a paired analysis of 26 women who completed both arms of the study,
acyclovir therapy was associated with a decrease in the frequency of s
ubclinical 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 red
uced at all anatomic sites and in all patients. Conclusions: Daily the
rapy with oral acyclovir suppresses subclinical shedding of HSV-2 in t
he genital tract, suggesting that studies to evaluate the use of acycl
ovir in preventing HSV-2 transmission are warranted.