Sexual transmission of herpes simplex virus type 2 (HSV-2) has been demonstrated from both symptomatic and asymptomatic reactivations in the infected partner. Daily antiviral therapy has been shown to decrease the frequency and amount of genital HSV shedding. Corey and colleagues tested daily valacyclovir for efficacy in preventing sexual transmission of HSV-2 from infected persons to their uninfected partners.
The study enrolled monogamous, immunocompetent, heterosexual couples in which only one partner was infected with HSV-2, as demonstrated by Western blot analysis of anti–HSV-2 serum antibodies. Of the initial 4,034 couples screened, 1,385 asymptomatic partners already had serologic evidence of HSV-2 infection and were ineligible, and 799 of the source partners were symptomatic but had negative HSV-2 serology. After informed consent, 352 couples declined to participate, and 14 persons declined to take the study medicines, leaving 1,484 couples (37 percent) available for randomization.
The infected source partner of each enrolled couple was randomized to receive valacyclovir in a dosage of 500 mg or placebo taken once daily for eight months. All couples were encouraged at each follow-up visit to use condoms. The medication dose was increased to twice daily for five days during any HSV-2 reactivation episode. A total of 1,159 couples (78.1 percent) were able to complete the entire eight-month protocol, with similar dropout rates in the active treatment and placebo groups (21 percent versus 23 percent).
During the eight-month trial, 71 susceptible partners developed genitourinary symptoms suggestive of HSV-2 transmission, but in 48 of these cases there was no serologic, viral culture, or DNA evidence of HSV-2 infection. The remaining 25 susceptible partners did have evidence of HSV-2 transmission, as did 18 asymptomatic patients. Overall, transmission of HSV-2 infection during the study was about one half as likely in the couples in which the source partner was taking daily valacyclovir (1.9 percent) as in couples receiving placebo (3.6 percent), which was a statistically significant reduction.
The number of source partners reporting at least one symptomatic genital recurrence during the study also was cut by about one half with use of daily valacyclovir (38.8 percent versus 77.3 percent). Four cases of HSV-1 transmission occurred in couples in which placebo was used, with no such cases in couples randomized to active treatment. In a subgroup of 89 couples who submitted genital swabs daily for two months, HSV-2 DNA was detected on 2.9 percent of days in source partners taking valacyclovir, compared with 10.8 percent of days when placebo was taken.
The authors conclude that daily valacyclovir halves the transmission rate of HSV-2 to an uninfected partner over an eight-month period.
editor’s note: This study confirms the substantial (although incomplete) protective benefits of daily viral suppression that have been reported in other trials of anti-herpes therapy. Whether the absolute risk reduction of 1.7 percent is worth the burden of taking daily medication for eight months is in the eye of the beholder. During this study, 66 monogamous couples dissolved their relationships. Perhaps the best use of viral suppression might be early in a relationship, when the long-term viability of the union is less clear, yet the risk for transmission is present on the many days when viral shedding occurs.—b.z.