Clinical trial NCT00530777: HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding
Official title: HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Herpes Simplex
Keywords: Disease Transmission, Vertical
valacyclovir
Randomized Controlled Trials
HIV
herpes
Herpesvirus 2, Human
HIV Seronegativity
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Royalty Research Fund - University of Washington
name: Puget Sound Partners for Global Health
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2007-09-17
Enrollment: 148
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change in HIV-1 Levels in Plasma Between 34 and 38 Weeks Gestation
timeFrame: 4 weeks
Secondary outcomes:
measure: Vertical HIV-1 Transmission
timeFrame: 1 year postpartum
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: Mathare North City Clinic
Study officials:
affiliation: University of Washington
name: Carey Farquhar, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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