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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HSV Infection, HIV Infection

Intervention / Treatment
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* Drug: acyclovir
* Drug: valacyclovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: acyclovir<br>acyclovir 400 mg orally twice daily | Drug: acyclovir<br>* acyclovir 400 mg orally, twice daily for 12 weeks<br>|
| Active Comparator: valacyclovir<br>valacyclovir 1.5 g orally twice daily | Drug: valacyclovir<br>* valacyclovir 1.5 g orally, twice daily, for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. | 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. | Weekly for 12 weeks per intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons. |  | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSV, HIV