Once daily valcyclovir slightly reduces the risk of transmitting HSV-2 to uninfected partners

Question Does daily valcyclovir reduce the risk of transmission of herpes simplex virus-2 (HSV-2) to uninfected sexual partners?

Synopsis Although we know that antiviral drugs reduce the frequency of recurrence, and also reduce subclinical shedding of viral particles (a disease oriented outcome), no trial to date has demonstrated an effect on the transmission of HSV-2 infection to an uninfected partner. In this randomised controlled (double blinded) trial, 1498 couples in which one partner was HSV-2 positive and one was HSV-2 negative were identified. The infected partner had to have had fewer than 10 recurrences per year and was not taking an antiviral drug for daily prophylaxis. Couples were heterosexual, claimed to be monogamous, and were advised to use condoms. The infected partner was randomised to valcyclovir 500 mg once daily or placebo, and non-infected partners underwent monthly HSV-2 serology. They were also asked to come in for polymerase chain reaction testing of genital secretions if they noticed any lesions. Patients were followed for a mean of eight months; 325 couples withdrew from the study during this period. The reasons for withdrawal were similar between groups, except that 28 withdrew voluntarily from the valcyclovir group and 54 from the placebo group, raising questions about either allocation concealment or blinding. Only 20% of couples used condoms all the time, and 37% never used them. The uninfected partner was less likely to acquire both symptomatic HSV-2 infection (0.5% v 2.2%; P = 0.008; absolute risk reduction (ARR) = 1.7%; number needed to treat (NNT) = 59) and any HSV-2 infection (1.9% v 3.6%; P = 0.04; ARR = 1.7%; NNT = 59) if their partner was taking valcyclovir. This study was sponsored by the manufacturer of valcyclovir.

Bottom line Once daily valcyclovir (Valtrex) slightly reduces the risk of transmission of herpes simplex virus 2 (HSV-2) to uninfected partners. Fifty nine patients have to take the drug daily for eight months to prevent one infection.

Level of evidence 1b (see www.infopoems.com/levels.html). Individual randomised controlled trials (with narrow confidence interval)