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Suppression of Subclinical Shedding of Herpes Simplex Virus Type 2 with Acyclovir

Anna Wald, MD, MPH; Judith Zeh, PhD; Gail Barnum, ARNP; L.G. Davis, PhD; and Lawrence Corey, MD
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From the University of Washington, Seattle, Washington, and Burroughs Wellcome Company, Research Triangle Park, North Carolina. Acknowledgments: The authors thank Drs. Jack Hill and David Koelle for performing acyclovir sensitivity testing on viral isolates. Grant Support: By NIH grant AI-30731 and by Burroughs Wellcome Company. Dr. Wald is a recipient of a postdoctoral research fellowship from the American Social Health Association. Requests for Reprints: Lawrence Corey, MD, University of Washington, Virology Division, Room 9301, 1200 12th Avenue South, Seattle, WA 98144. Current Author Addresses: Dr. Wald: Virology Research Clinic, 1001 Broadway, Suite 320, Seattle, WA 98122.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(1_Part_1):8-15. doi:10.7326/0003-4819-124-1_Part_1-199601010-00002
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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.


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Figure 1.
Time to first subclinical shedding of HSV among 34 women during the initial arm of the study.
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Figure 2.
Comparison of number of days during which lesions were noted among 26 women while they were receiving placebo and acyclovir therapy.
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Figure 3.
Comparison of total herpes simplex virus shedding rates among 26 women while they were receiving placebo and acyclovir therapy.
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