Examining the Ability of Herpes Simplex Virus Type 2 (HSV2) Therapy to Reduce HIV Target Cell Numbers in the Cervix

Study Overview
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Brief Summary
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Herpes simplex virus type 2 (HSV2), the most common cause of genital herpes, increases a woman's risk of HIV acquisition from 3-6 fold, perhaps because HSV2-infected women have increased numbers of HIV target cells (CD4 T cells and dendritic cells) in the cervical mucosa. However, recent clinical trials showed no impact of HSV2 suppression on HIV acquisition rates. The reasons for this negative result are unclear. The investigators propose to examine the effect of valacyclovir (a widely used herpes medication) treatment on cervical immunology and HIV target cells in the cervix. The study will take the form of a randomized, double-blind, placebo-controlled crossover trial. Primary endpoints will be (1) the number of CD4 T cells on a cervical cytobrush and (2) the number of immature dendritic cells per cervical cytobrush.

Official Title
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Examining the Ability of HSV2 Therapy to Reduce HIV Target Cell Numbers in the Cervix.

Conditions
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Herpes Simplex Type Two Infection, HIV Infections

Intervention / Treatment
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* Drug: Valacyclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female HSV2 infected Exclusion Criteria: HIV infected Pregnant Taking HSV2 therapy Current/recent (past 3 months) genital infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will be assigned 2 months of placebo or active drug, with an intervening one month washout period. | Drug: Valacyclovir<br>* 1g po od for 2 months<br>Drug: Placebo<br>* Placebo po od for 2 months<br>|
| Experimental: Valacyclovir<br>Participants will be assigned 2 months of placebo or active drug, with an intervening one month washout period. | Drug: Valacyclovir<br>* 1g po od for 2 months<br>Drug: Placebo<br>* Placebo po od for 2 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CD4+ T cells on a cervical cytobrush. |  | Monthly intervals for 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of immature dendritic cells on a cervical cytobrush |  | Monthly intervals for 5 months | 
| Proinflammatory cytokine/chemokine levels in cervicovaginal secretions |  | Monthly intervals for 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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herpes simplex virus type 2, HIV, genital immunology, CD4+ T cell, valacyclovir, HIV seronegativity