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

Condition(s) targeted: HIV Infections; Herpes Simplex

Intervention: valacyclovir (Drug); placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Carey Farquhar, MD, MPH, Principal Investigator, Affiliation: University of Washington

Overall contact:
Alison L Drake, MPH, Phone: 206-579-9211, Email: adrake2@u.washington.edu

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: HIV-1 levels in plasma, genital tract, and breast milk

Secondary outcome:

Vertical HIV-1 transmission

antenatal cervical HSV-2 levels

Maternal Creatinine and infant ALT and creatinine levels

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 transmission of HIV-1 infection.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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

Alison L Drake, MPH, Phone: 206-579-9211, Email: adrake2@u.washington.edu

Mathare North City Clinic, Nairobi, Kenya; Recruiting
James Kiarie, MMed, MPH, Phone: 254-20-2714159, Email: jkiarie@swiftkenya.com
Carey Farquhar, MD, PMH, Principal Investigator
James Kiarie, MMed, MPH, Principal Investigator
Barbra Richardson, PhD, Principal Investigator
Alison L Drake, MPH, Principal Investigator

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Starting date: April 2008
Ending date: September 2009
Last updated: October 9, 2008