Hindawi Publishing Corporation Infectious Diseases in Obstetrics and Gynecology Volume 2009, Article ID 105376, 7 pages doi:10.1155/2009/105376 Clinical Study Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes Mark G. Martens,1 Kenneth H. Fife,2 Peter A. Leone,3 Lynn P. Dix,4 and Clare A. Brennan4 1 Planned Parenthood of Arkansas and Eastern Oklahoma, Inc., 5780 S. Peoria Ave, Tulsa, OK 74105, USA 2 Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN 46202, USA 3 Division of Infections Diseases, University of North Carolina, Chapel Hill, NC 27599, USA 4 GlaxoSmithKline, Research Triangle Park, NC 27709, USA Correspondence should be addressed to Mark G. Martens, mgmartens@aol.com Received 26 March 2009; Accepted 17 June 2009 Recommended by Jane R. Schwebke Objective. Genital herpes (GH) recurrences and viral shedding are more frequent in the ﬁrst year after initial HSV-2 infection. The objective of this study was to provide the ﬁrst evaluation of valacyclovir 1 g once daily compared to placebo in reducing viral shedding in subjects newly diagnosed with GH. Methods. 70 subjects were randomized to receive valacyclovir 1 g daily or placebo in a crossover design for 60 days with a 7-day washout period. A daily swab of the genital/anal-rectal area was self-collected for HSV-2 detection by PCR. Subjects attended the clinic for routine study visits and GH recurrence visits. Treatment diﬀerences were assessed using a nonparametric crossover analysis. Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary eﬃcacy population. Valacyclovir signiﬁcantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P < .01), a 78% reduction). Valacyclovir signiﬁcantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P < .01), a 78% reduction). However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P < .01). Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the ﬁrst to demonstrate a signiﬁcant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection. Copyright © 2009 Mark G. Martens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction Genital herpes is most commonly caused by infection with herpes simplex virus type 2 (HSV-2), and is one of the most prevalent sexually transmitted diseases (STD) worldwide [1– 3]. The incidence of new infections is about 1 million cases per year in the United States [4]. At least 50 million persons in the United States have HSV-2 infection [5]. However, 86% of these individuals are unaware of their diagnosis, either because they do not have symptoms or because they have symptoms that go unrecognized [3, 6]. Previous studies demonstrated both viral shedding and recurrences are more frequent in the ﬁrst year after initial HSV-2 infection [7–11]. In one natural history study, women who acquired genital herpes within a year before enrollment had more frequent shedding compared to women who had been infected for one year or more [8]. Another study found that individuals diagnosed for ≤6 months were twice as likely to shed asymptomatically compared to those diagnosed for more than 6 months [11]. Collectively, higher viral shedding and recurrence rates in subjects with newly acquired infection may translate to an increased risk of transmitting virus to uninfected sex partners. In studies of immunocompetent adults with a known recurrence pattern, HSV-2 DNA as detected by polymerase chain reaction (PCR) testing was present on approximately 10% of days [12, 13]. Several investigations have supported the eﬀect of suppressive antiviral therapy on the reduction of viral shedding in patients with an established recurrence pattern [9, 11, 14–17]. More recent studies have shown that suppressive antiviral therapy is as eﬀective at controlling symptomatic disease in recently infected persons as it is