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Previous Volume 350:11-20 January 1, 2004 Number 1 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Crumpacker, C. S. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Nucleoside analogues against herpes simplex virus (HSV) have been shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and may prevent sexual transmission of HSV.

Methods We followed 1484 immunocompetent, heterosexual, monogamous couples: one with clinically symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2 infection were randomly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months. The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes. Source partners were followed for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2 mucosal shedding. Both partners were counseled on safer sex and were offered condoms at each visit. The predefined primary end point was the reduction in transmission of symptomatic genital herpes.

Results Clinically symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir, as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir (1.9 percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio, 0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected in samples of genital secretions on 2.9 percent of the days among the HSV-2–infected (source) partners who received valacyclovir, as compared with 10.8 percent of the days among those who received placebo (P<0.001). The mean rates of recurrence were 0.11 per month and 0.40 per month, respectively (P<0.001).

Conclusions Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual, HSV-2–discordant couples.

Source Information

From the Departments of Medicine (L.C., A.W.), Laboratory Medicine (L.C., R.A.M.), and Epidemiology (A.W.), University of Washington, Seattle; the Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle (L.C.); the Department of Genitourinary Medicine, Royal South Hants Hospital, Southampton, United Kingdom (R.P.); Viridae Clinical Sciences and University of British Columbia, Vancouver, Canada (S.L.S.); the University of Texas Medical Branch, Galveston (S.K.T.); Westover Heights Clinic, Portland, Oreg. (T.W.); the Disease Control Service, Denver Department of Public Health, Denver (J.M.D.); the Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland (J.P.); Dow Pharmaceutical Sciences and Department of Dermatology, University of California, San Francisco (K.R.B.); the Department of Clinical Pharmacology, Smolensk State Medical Academy, Smolensk, Russia (L.S.S.); the Department of Medicine, University of New Mexico, Albuquerque (G.M.); and the Departments of Biomedical Data Sciences (O.N.K.) and Antiviral Clinical Research (H.A.W., D.T., M.V.-C.), GlaxoSmithKline Research and Development, Greenford, United Kingdom.

Address reprint requests to Dr. Corey at the Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Rm. D3-100, P.O. Box 19024, Seattle, WA 98109, or at lcorey{at}u.washington.edu.

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