HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1 Co-Infected Persons

• Mucosal HSV-2 shedding [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
• Determine the temporal pattern of HIV shedding with respect to HSV-1 and HSV-2 reactivation; [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

• Evaluate HSV-2 suppression with decreased plasma HIV RNA levels;
• Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals;
• Determine the temporal pattern of HIV shedding with respect to HSV-1 and HSV-2 reactivation;
• Determine HSV-2 suppression and HIV replication.

Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that HSV is an important co-factor in HIV transmission.

The trial's purpose is to assess the reduction in HIV systemic and mucosal replication associated with valacyclovir for suppression of HSV-2 reactivation.

This randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected women assessed the effects of daily valacyclovir on HIV-1 levels in blood and body fluids.

Conducted in Lima Peru, 20 HIV-1 and HSV-2 seropositive women with CD4 counts greater than 200 and on no antiretroviral therapy were randomly assigned to receive valacyclovir 500 mg bid or placebo for the first 8 weeks of the study. After these 8 weeks, a 2-week washout period followed, which was then followed by the alternative regimen for 8 weeks.

• HIV Infections
• Herpes Simplex
• Sexually Transmitted Diseases

• Drug: Valacyclovir
  500mg oral twice daily
  Other Name: Valtrex
• Drug: Matching Placebo
  500 mg oral twice daily
  Other Name: Placebo for Valacyclovir

Inclusion Criteria:

• Greater than 18 years old woman,
• Documented HIV-1 seropositive,
• CD4 count greater than 200,
• Not on HIV antiretroviral therapy,
• HSV-2 seropositive as determined by Focus EIA (IN >3.5)
• Not intending to move out of the area for the duration of study participation.
• Willing and able to:provide independent written informed consent;undergo clinical evaluations;take study drug as directed;adhere to follow-up schedule.
• Bacterial STDs (symptomatic STD syndromes or laboratory-confirmed asymptomatic gonorrhea and syphilis) are treated within two weeks of study enrollment and random assignment.

Exclusion Criteria:

Women who meet any of the following criteria are not eligible for this study:

• Known history of adverse reaction to valacyclovir, acyclovir or famciclovir;
• Planned open label use of acyclovir, valacyclovir, or famciclovir
• Known medical history of seizures
• Known renal failure, serum creatinine >2.0mg/dl
• Hematocrit < 30 %

• GlaxoSmithKline
• Asociación Civil Impacta Salud y Educación, Peru