A LARGE-SCALE, PLACEBO-CONTROLLED, DOSE-RANGING TRIAL OF PERORAL VALACICLOVIR FOR EPISODIC TREATMENT OF RECURRENT HERPES GENITALIS

Background: Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir it self and is rapidly and completely converted to acyclovir by the liver . Accordingly, valaciclovir has the same antiviral activity as acyclov ir, but the potential for enhanced clinical activity and/or less frequ ent administration because of its superior pharmacokinetics. Methods: We conducted a double-blind, placebo-controlled, patient-initiated cli nical trial of peroral valaciclovir, 500 or 1000 mg, or matching place bo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results: Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [CI], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in compa rison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CT, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (haz ard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral sh edding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among t he valaciclovir groups were comparable with those of the placebo group . Conclusions: Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesion s, the duration of pain or discomfort, and the duration of virus shedd ing. In addition, this study, to our knowledge, provides the first con vincing demonstration that antiviral therapy can prevent lesion develo pment. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genital is.