HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding

Study Overview
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Brief Summary
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In this study, we will determine whether treating pregnant and breastfeeding women co-infected with human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) with daily valacyclovir will reduce HIV-1 levels in plasma, genital, and breast milk and will decrease the risk of mother-to-child HIV-1 transmission (MTCT).

Detailed Description
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Each year over 500,000 children become HIV-1-infected in sub-Saharan Africa after exposure to maternal virus in blood, genital secretions, and breast milk. Identifying feasible, safe, and affordable interventions that prevent mother-to-child transmission remains a priority for HIV-1 prevention research. Interventions to reduce breast milk HIV-1 transmission are lacking and most urgently needed. We propose a randomized clinical trial to determine whether incorporating HSV-2 suppression with valacyclovir into standard prevention of mother-to-child HIV-1 transmission regimens will reduce plasma, cervical, and breast milk HIV-1 RNA levels and risk of transmission among HIV-1-infected and HSV-2-seropositive women. We plan to enroll a total of 148 HIV-1 and HSV-2 co-infected pregnant women with CD4>200 cells/μl who seek antenatal care prior to 32 weeks gestation at a clinic in Nairobi, Kenya. Women will be randomized to receive either valacyclovir suppressive therapy or placebo at 34 weeks gestation and mother-infant pairs will be followed for 12 months postpartum. Follow-up visits will be scheduled at 38 weeks gestation; birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months postpartum. Maternal blood, genital, and breast milk specimens obtained at follow-up visits will be used to determine the effect of valacyclovir suppressive therapy on plasma and breast milk HIV-1 RNA levels. Infant filter paper specimens for HIV-1 DNA assays will be collected at birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months in order to compare the proportion of infants acquiring HIV-1 by 12 months in the two study arms and determine the timing of HIV-1 infection. In addition, we will monitor maternal and infant renal function in preparation for a larger randomized clinical trial in Africa. The results of this study will help guide the design of a multi-site clinical trial with adequate power to determine the effect of HSV-2 suppression on vertical (MTCT) transmission of HIV-1 infection.

Official Title
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HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding

Conditions
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HIV Infections, Herpes Simplex

Intervention / Treatment
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* Drug: valacyclovir
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 seropositive HSV-2 seropositive Plans to deliver in Nairobi Resides and plans to remain in Nairobi for 12 months postpartum 18 years of age or older CD4 count>250 cells/μl Exclusion Criteria: indication for highly active antiretroviral therapy (e.g., WHO stage III or IV) hypersensitivity to valacyclovir or acyclovir

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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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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum | Drug: valacyclovir<br>* 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum<br>* Other names: Valtrex;|
| Placebo Comparator: 2<br>oral placebo twice daily from 34 weeks gestation to 1 year postpartum | Drug: placebo<br>* oral placebo twice daily from 34 weeks gestation to 1 year postpartum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in HIV-1 Levels in Plasma Between 34 and 38 Weeks Gestation | Calculated as log10 plasma viral load at 34 weeks gestation - log10 plasma viral load at 38 weeks gestation | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vertical HIV-1 Transmission | Mother-to-child HIV transmission | 1 year postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Disease Transmission, Vertical, valacyclovir, Randomized Controlled Trials, HIV, herpes, Herpesvirus 2, Human, HIV Seronegativity