• To determine the effect of suppressive antiviral therapy on sexual behavior among HSV-2 seropositive persons with multiple sexual partners. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

• To examine the acceptability and adherence to suppressive antiviral therapy for HSV-2 prevention among single, sexually active men and women. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

We plan to conduct a randomized controlled trial of chronic suppressive acyclovir, 400 mg orally twice daily (standard dose) versus episodic acyclovir for treatment of genital herpes recurrences. We will enroll 500 HSV-2 seropositive single persons (250 per arm), stratified by gender and history of symptomatic genital herpes, and prospectively follow them for 1 year to assess sexual behavior, adherence to therapy, and herpes-related quality of life. These outcomes will be measured by self-report in a confidential, computer-based assessment. We plan to use data from this trial to model the effect that increasing the proportion of sexually-active HSV-2 infected persons taking suppressive therapy will have on population-level incidence and prevalence of HSV-2.

Inclusion Criteria:

• Age 18 years or older
• HSV-2 seropositive by Western blot OR documented culture positive for HSV-2 from anogenital site
• 2 or more vaginal or anal sex partners in the past 12 months
• Not currently in a monogamous sexual relationship of >= 6 months duration
• Willing and able to be randomized and comply with the study protocol

Exclusion Criteria:

• Pregnancy or intention to become pregnant within the next year
• Suppressive therapy with acyclovir, valacyclovir, or famciclovir within 2 weeks of enrollment/randomization
• 6 or more symptomatic herpes recurrences in the prior 12 months or in the 12 months prior to starting suppressive therapy if on suppressive therapy during the prior 12 months
• HIV seropositive or known immunocompromising medical condition. HIV negative test must be performed within 60 days of Visit 1 (enrollment/randomization). For current or former participants in HIV vaccine clinical trials for whom HIV vaccine-induced seropositivity potentially leading to vaccine study unblinding may be a concern, a report from the Seattle HVTU documenting that the participant is HIV uninfected based on HIV testing done within 60 days of Visit 1 will be accepted in lieu of HIV testing done at our clinic.
• Intention to move from the Seattle area within the next year
• Known allergy, intolerance, or medical contraindication to acyclovir
• Inability to understand, speak, and read English