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

Official Title: “A Randomized, Open-label, Crossover Trial of the Effect of High-dose Daily HSV-2 Suppressive Therapy on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons”

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.

Intervention(s) in this Clinical Trial

• Drug: acyclovir
  • Acyclovir 400 mg orally, twice daily for 12 weeks
• Drug: Valacyclovir
  • valacyclovir 1.5 g orally, twice daily, for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Acyclovir
  • Acyclovir 400 mg orally twice daily
• Active Comparator: Valacyclovir
  • Valacyclovir 1.5 g orally twice daily

Primary Measures

• Presence and quantity of the 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.
  • Time Frame: 28 weeks
    Safety Issue?: No

Secondary Measures

• Evaluate the safety of valacyclovir 1.5 gram orally twice daily in HIV-1 seropositive persons.
  • Time Frame: 28 weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Washington Other

Overall Clinical Trial Officials and Contacts

Connie Celum, MD, MPH Principal Investigator University of Washington  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01026454

Study ID Number: 37162-A

ClinicalTrials.gov Identifier: NCT01026454

Health Authority: United States: Institutional Review Board