Effect of valacyclovir on viral shedding in immunocompetent patients with recurrent herpes simplex virus 2 genital herpes: a US-based randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To determine the efficacy of daily suppressive therapy with a 1-g dose of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus 2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes. PATIENTS AND METHODS: From June 18, 2004, to December 17, 2004, patients from 27 US sites with a history of 6 or more genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1 g/d of valacyclovir or placebo. During the double-blind suppressive therapy, patients were provided with the study drug (500-mg valacyclovir caplets or matching placebo) and Instructed to take 2 caplets once daily without regard to meals for 60 days. Daily genital and anal or rectal swabs were self-collected during the 60-day study period for evaluation of HSV-2 viral shedding as determined by quantitative type-specific polymerase chain reaction assay. RESULTS: One hundred fifty-two patients were randomized into this study, 43 to placebo and 109 to 1 g/d of valacyclovir. A total of 134 completed the study (40 placebo [93%], 94 valacyclovir [86%]), and 18 prematurely withdrew (3 placebo [7%], 15 valacyclovir [14%]). Valacyclovir significantly reduced the percentage of days with total (clinical and subclinical) HSV-2 shedding throughout 60 days compared with placebo. In the intent-to-treat population, a 71% reduction in total shedding (P < .001), a 58% reduction in subclinical shedding (P < .001), and a 64% reduction in clinical shedding (P = .01) were observed. Valacyclovir was not associated with any significant toxic effects compared with placebo. CONCLUSION: This study demonstrated that 1 g/d of valacyclovir administered for 60 days was generally well tolerated and was an effective suppressive therapy that significantly reduced total (clinical and subclinical) HSV-2 shedding compared with placebo in immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes.

An international, randomized, double-blind, placebo-controlled, study of valacyclovir for the suppression of herpes simplex virus type 2 genital herpes in newly diagnosed patients.

BACKGROUND: Antiviral suppressive therapy of genital herpes is often initiated based on the established pattern of recurrences in an individual. Because most persons with first episode herpes simplex virus type 2 (HSV-2) infection experience recurrences and because viral shedding occurs frequently in the first year after infection, we examined the strategy of initiating suppressive therapy shortly after diagnosis of genital HSV-2 infection. SUBJECTS AND METHODS: From June 16, 2004 to July 26, 2006, 384 subjects from 74 sites in the United States, Canada, Argentina, Brazil, and Chile who were newly diagnosed with a first recognized episode of genital herpes at the time of the screening visit or within 3 months before the screening visit were randomized (2:1) to receive valacyclovir 1 g once daily or placebo for 24 weeks. Subjects were instructed to return to clinic during suspected genital herpes outbreaks for clinician confirmation of recurrences. RESULTS: Valacyclovir significantly prolonged the time to first recurrence of HSV-2 genital herpes in newly diagnosed subjects compared with placebo, with approximately 43% of subjects on placebo and 71% of subjects on valacyclovir recurrence-free at 24 weeks (P <0.001). Valacyclovir significantly reduced the mean number of genital HSV-2 recurrences per month occurring during the 24-week study period (0.11 for valacyclovir, 0.48 for placebo, P <0.001). Adverse events were comparable in the valacyclovir and placebo arms. CONCLUSION: Valacyclovir 1 g once daily administered for 24 weeks was well-tolerated and effective in suppressing genital herpes recurrences in immunocompetent newly diagnosed persons without an established recurrence pattern.

The effect of daily valacyclovir suppression on herpes simplex virus type 2 viral shedding in HSV-2 seropositive subjects without a history of genital herpes.

BACKGROUND: A substantial number of HSV-2 seropositive individuals lack a history of clinically recognized genital herpes. These individuals can transmit disease during periods of asymptomatic viral shedding. The frequency of asymptomatic shedding and the efficacy of antiviral therapy in reducing shedding has not been assessed in this population. OBJECTIVE: To compare the effect of valacyclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. STUDY DESIGN: Seventy-three subjects were randomized to receive valacyclovir 1 g daily or placebo for 60 days each in a 2-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction. RESULTS: Fifty-six subjects with at least 1 polymerase chain reaction measurement in both treatment periods comprised the primary efficacy population. Valacyclovir significantly reduced shedding during subclinical days compared to placebo [mean, 1.5% vs. 5.1% of subclinical days (P <0.001), a 71% reduction]. Eighty-four percent of subjects had no shedding while receiving valacyclovir versus 54% of subjects on placebo (P <0.001). Eighty-eight percent of patients receiving valacyclovir had no recognized signs or symptoms versus 77% for placebo (P = 0.033). Valacyclovir was not associated with any safety risk compared with placebo. CONCLUSIONS: In this study, asymptomatic viral shedding occurred in a substantial number of HSV-2 seropositive subjects without a history of genital herpes. Valacyclovir 1 g daily significantly reduced asymptomatic shedding compared with placebo in this population.