Valacyclovir vs. Acyclovir as HSV-2 Suppressive Therapy: Effect on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons

Phase 4

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
acyclovir	acyclovir	acyclovir 400 mg orally twice daily
valacyclovir	valacyclovir	valacyclovir 1.5 g orally twice daily

Primary Outcome Measures

Name	Time	Method
Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir.	Weekly for 12 weeks per intervention	Mean level of HIV-1 RNA in plasma of participants while on 400 mg twice daily of acyclovir versus while on 1.5 g twice daily of valacyclovir.

Secondary Outcome Measures