The purpose of this study is to determine whether treating HSV-2 with either valacyclovir or acyclovir is more effective in suppressing HIV-1 virus levels in people co-infected with HIV-1 and HSV-2.

Sexual transmission is responsible for the vast majority of HIV-1 infections among adults worldwide. In sub-Saharan Africa, the region hardest hit by the HIV-1 epidemic, HSV-2 prevalences of 30-50% have been seen in the general population with prevalence up to 90% in infected with HIV-1. HSV-2 is common in those with, or at risk for, HIV-1 infection, and HSV-2 reactivation increases HIV-1 acquisition and infectiousness. Recent studies have shown that suppression of HSV-2 has a sustained effect on lowering HIV-1 levels in blood plasma. New data have raised the question whether higher doses of HSV-2 suppressive therapy might be more effective at suppressing HIV-1 levels. Acyclovir and valacyclovir, chosen for use in this study, are safe and effective treatments for decreasing the frequency of HSV-2 reactivation and shedding. The standard dose of acyclovir is 400 mg twice a day. Valacyclovir, a drug that converts to acyclovir after absorption, delivers higher concentrations of acyclovir. 1.5 grams of valacyclovir, will be used to provide a higher dose of acyclovir, and will be compared with the standard dose of 400 mg twice a day of acyclovir.

Inclusion Criteria:

• HIV-1 seropositive
• Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
• CD4 cell count >250 cell/µL
• Not otherwise eligible for antiretroviral therapy according to Uganda national guidelines
• Detectable HIV-1 plasma viral load
• HSV-2 seropositive
• Not intending to move out of the area for the duration of study participation.
• Able to participate in the study at the Partners in Prevention site in Thika, Kenya

Exclusion Criteria:

• Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir.
• Planned use of acyclovir, valacyclovir, or famciclovir
• Use of ganciclovir, foscarnet, or cidofovir
• Known medical history of seizures
• Serum creatinine >1.5 mg/dL
• AST or ALT >3 times upper limit of normal
• Hematocrit <30 %
• Absolute neutrophil count <1000
• Platelet count <75,000
• History of thrombotic microangiopathy
• Any other condition which, in the opinion of the principal investigator, may compromise the ability to follow study procedures and complete the study
• Participation in another HIV therapeutics trial
• For women, pregnancy as confirmed by a urine pregnancy test

28 weeks