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

University of Washington

Status and phase: Completed; Phase 2

Conditions: Herpes Simplex; HIV Infections

Treatments: Drug: valacyclovir; Drug: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00530777

R03HD057773 (U.S. NIH Grant/Contract)

32462

07-7306-A01

Details and patient eligibility

About

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).

Full 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.

Enrollment: 148 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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148 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum

Treatment:

Drug: valacyclovir

2

Placebo Comparator group

Description:

oral placebo twice daily from 34 weeks gestation to 1 year postpartum

Treatment:

Drug: placebo