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.


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.


CONCLUSIONS
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.
Fife
Kenneth H
KH
Indiana University School of Medicine, Room 435 Emerson Hall, 545 Barnhill Dr, Indianapolis, IN 46202, USA. kfife@iupui.edu
Warren
Terri J
TJ
Ferrera
R David
RD
Young
Douglas G
DG
Justus
Scott E
SE
Heitman
Catherine K
CK
Burroughs
Scott M
SM
D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D014481:United States; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017201:Virus Shedding / Q000187:drug effects*
D000998:Antiviral Agents; D011355:Prodrugs; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir