Once-daily valacyclovir to reduce the risk of transmission of genital herpes.
BACKGROUND
Nucleoside analogues against herpes simplex virus (HSV) have been shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and may prevent sexual transmission of HSV.


METHODS
We followed 1484 immunocompetent, heterosexual, monogamous couples: one with clinically symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2 infection were randomly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months. The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes. Source partners were followed for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2 mucosal shedding. Both partners were counseled on safer sex and were offered condoms at each visit. The predefined primary end point was the reduction in transmission of symptomatic genital herpes.


RESULTS
Clinically symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir, as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir (1.9 percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio, 0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected in samples of genital secretions on 2.9 percent of the days among the HSV-2-infected (source) partners who received valacyclovir, as compared with 10.8 percent of the days among those who received placebo (P<0.001). The mean rates of recurrence were 0.11 per month and 0.40 per month, respectively (P<0.001).


CONCLUSIONS
Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual, HSV-2-discordant couples.
Corey
Lawrence
L
Department of Medicine, University of Washington, Seattle, USA. lcorey@u.washington.edu
Wald
Anna
A
Patel
Raj
R
Sacks
Stephen L
SL
Tyring
Stephen K
SK
Warren
Terri
T
Douglas
John M
JM
Paavonen
Jorma
J
Morrow
R Ashley
RA
Beutner
Karl R
KR
Stratchounsky
Leonid S
LS
Mertz
Gregory
G
Keene
Oliver N
ON
Watson
Helen A
HA
Tait
Dereck
D
Vargas-Cortes
Mauricio
M
D000212:Acyclovir / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000635:transmission; D018258:Herpesvirus 2, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D021841:Safe Sex; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D014775:Virus Activation / Q000187:drug effects
D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir