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Does Frequency of Genital Herpes Recurrences Predict Risk of Transmission? Further Analysis of the Valacyclovir Transmission Study

Kim, H Nina MD, MS*; Wald, Anna MD, MPH*†‡; Harris, Julia MA§; Almekinder, Jennifer BS§; Heitman, Cathy PhD§; Corey, Lawrence MD*‡∥

doi: 10.1097/OLQ.0b013e31815407d7

Background: The benefit of suppressive antiviral therapy for reducing the risk of herpes simplex virus (HSV)-2 transmission to sex partners may be enhanced if persons at high risk for transmission can be identified.

Objective: To determine whether frequency of genital herpes recurrences is associated with increased risk of HSV-2 transmission.

Methods: Analysis of recurrence frequency and shedding frequency (subset) among participants in a randomized controlled trial of valacyclovir 500 mg qd versus placebo for reducing the risk of HSV-2 transmission.

Results: Overall, 1484 monogamous HSV-2-serodiscordant couples participated and 41 HSV-2 transmissions occurred during the 8-month trial; 40 were able to provide a history of recurrence frequency. The rate of recurrences per year before study entry did not differ between source partners who transmitted and those who did not, 4.8 versus 5.1, respectively. Similarly, the mean frequency of recurrences observed during the study also did not differ among those who transmitted versus those who did not for placebo recipients (4.4 vs. 4.8) or valacyclovir recipients (1.4 vs. 1.3). Among the 40 source partners who transmitted HSV-2, 8 of 27 placebo recipients and 7 of 13 valacyclovir recipients had no recurrences during the study.

Conclusion: Clinical assessment of HSV-2 disease severity as defined by the frequency of genital herpes recurrences does not predict the risk of transmission to sexual partners. Though patients with frequent recurrences are most likely to benefit clinically from suppressive therapy, frequency of recurrences is not helpful in identifying persons who are most likely to transmit HSV-2.

Further analysis of a randomized controlled trial of daily valacyclovir versus placebo for reducing the risk of herpes simplex virus-2 transmission shows that the frequency of genital herpes recurrences does not predict the risk of transmission to sexual partners.

From the *Department of Medicine, Division of Allergy and Infectious Diseases; †Department of Epidemiology; ‡Department of Laboratory Medicine, University of Washington, Seattle, Washington; §GlaxoSmithKline, Triangle Park, North Carolina; and ∥Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington

Supported by GlaxoSmithKline, National Institutes of Health Herpes Program Project grant AI-030731 and K24 AI-071113. The University of Washington Virology Division has received grant funding from GlaxoSmithKline and Novartis pharmaceuticals to perform HSV testing.

Presented in part at the 2006 National STD Prevention Conference, Centers for Disease Control and Prevention Meeting; May 10, 2006; Jacksonville, FL. Abstract 227.

A.W. is a consultant for Novartis, Powdermed, and Medigene and a speaker for Merck Vaccines. A.W. has received grant support from National Institutes of Health, GlaxoSmithKline, Antigenics, 3M, Roche, and Vical. J.H., J.A. and C.H. receive salaries from GlaxoSmithKline. L.C. directs the Division but receives no direct salary support for these activities. He has been a consultant to Antigenics in their program to develop an HSV vaccine.

Correspondence: H. Nina Kim, MD, MS, 901 Boren Avenue, Suite 1300, Seattle, WA 98104. E-mail:

Received for publication March 21, 2007, and accepted July 12, 2007.

© Copyright 2008 American Sexually Transmitted Diseases Association