Study to Improve Survival Among HIV-Exposed Infants in Botswana

Phase 2

Completed

• Conditions: Anemia; HIV Infections; Neutropenia
• Interventions: Behavioral: breastfeeding for 12 months; Drug: cotrimoxazole prophylaxis; Behavioral: exclusive breastfeeding until 6 months of age; Drug: cotrimoxazole placebo

• Registration Number: NCT01229761
• Lead Sponsor: Harvard School of Public Health (HSPH)

Brief Summary

The purpose of this study is to find ways to improve infant health and survival among infants whose mothers are HIV-infected but who do not themselves have HIV.

Detailed Description

As improved MTCT prevention interventions reduce the number of HIV-infected infants in the antepartum and peripartum periods, interventions to improve HIV-free survival among HIV-uninfected infants are needed. Morbidity and mortality are increased among HIV-uninfected infants born to HIV-infected mothers, and reduced infant survival among HIV-exposed infants may lead to as many deaths as HIV infection itself. In Botswana, the use of formula feeding or shorter breastfeeding may worsen the problem of early infant mortality among HIV-exposed infants.

The study will enroll pregnant or postpartum HIV-1-infected women, and their HIV-uninfected infants in Botswana. At 2-4 weeks of age, live HIV-uninfected infants will be randomized to receive either double-blinded cotrimoxazole (CTX) or placebo from 2-4 weeks through 15 months. In addition, breastfeeding (BF) infants will be randomized to BF until either 6 or 12 months of age. Children will be followed prospectively until 18 months of age. The primary endpoint will be survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of BF among those BF at randomization. Secondary endpoints will evaluate survival and morbidity/mortality at 12 and 15 months; HIV-free survival to 18 months; and the safety of CTX prophylaxis. Secondary observational objectives include comparing MTCT and mortality by initial feeding method (formula feeding or any BF \> 1 month), and an analysis of maternal characteristics as predictors for initial feeding choice and HIV-free survival. All women and infants will receive standard antenatal and peripartum prophylaxis from the Botswana government for MTCT prevention (PMTCT), and will choose a feeding method with counseling. Breastfeeding infants will receive infant nevirapine (NVP) prophylaxis or will be protected from MTCT by the use of maternal HAART.

Study Timeline

• Study First Submitted: 2010-10-22
• Study First Submitted QC: 2010-10-26
• Study First Posted: 2010-10-28
• Study Start: 2011-05
• Primary Completion: 2015-03
• Study Completion: 2018-10
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 3724

Inclusion Criteria

• HIV-infected women, > 26 weeks gestation and < 34 days postpartum.
• Women must be ¬> 18 years of age and willing/able to sign informed consent.
• Women and infants must be able to follow up regularly at a study clinic through 18 months postpartum.
• For Feeding Randomization Only: Women must be willing to breastfeed for up to 12 months, and to stop at 6 months, depending upon their feeding assignment.

Exclusion Criteria

• Antepartum women: Known infant anomalies resulting in a high probability that the infant will not survive to 18 months.
• Postpartum women: Known HIV-infected infant, or infant medical condition making survival to 18 months unlikely.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
exclusive breastfeeding for 12 months	breastfeeding for 12 months	-
infant cotrimoxazole	cotrimoxazole prophylaxis	-
exclusive breastfeeding for 6 months	exclusive breastfeeding until 6 months of age	-
infant placebo	cotrimoxazole placebo	-

Primary Outcome Measures

Name	Time	Method
Survival	18 months of age	The primary outcome measure is survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of breastfeeding among those breastfeeding at randomization.

Secondary Outcome Measures

Name	Time	Method
HIV-free Survival	18 months of age	Secondary outcome measures will evaluate HIV-free survival between 4 weeks and 18 months among infants randomized to either 6 months or 12 months of breastfeeding.
Morbidity and mortality	18 months of age	Secondary outcome measures will evaluate morbidity and mortality to 18 months.
Safety of CTX prophylaxis	18 months	Secondary outcome measures will evaluate the safety of CTX prophylaxis through 18 months

Trial Locations

Locations (3)

Princess Marina Hospital; 🇧🇼 Gaborone, Botswana

Scottish Livingstone Hospital; 🇧🇼 Molepolole, Botswana

Athlone Hospital; 🇧🇼 Lobatse, Botswana