Clinical trial NCT01229761: Study to Improve Survival Among HIV-Exposed Infants in Botswana
Official title: A Randomized Study of Cotrimoxazole Prophylaxis and Longer Breastfeeding Duration to Improve Survival Among HIV-Exposed Infants in Botswana
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Neutropenia
Anemia
Keywords: HIV
Trimethoprim-Sulfamethoxazole Combination
Breast Feeding
Infant Mortality
Morbidity
Botswana
Africa
Infectious disease transmission, vertical
adverse drug event
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: Harvard Medical School (HMS and HSDM)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2010-10-28
Enrollment: 3724
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: 18 months of age
Secondary outcomes:
measure: HIV-free Survival
timeFrame: 18 months of age
measure: Safety of CTX prophylaxis
timeFrame: 18 months
measure: Morbidity and mortality
timeFrame: 18 months of age
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Princess Marina Hospital
city: Lobatse
country: Botswana
facility: Athlone Hospital
city: Molepolole
country: Botswana
facility: Scottish Livingstone Hospital
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Shahin Lockman, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard School of Public Health (HSPH)
name: Roger L Shapiro, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Powis KM, Souda S, Lockman S, Ajibola G, Bennett K, Leidner J, Hughes MD, Moyo S, van Widenfelt E, Jibril HB, Makhema J, Essex M, Shapiro RL. Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV-exposed infants in a randomized controlled trial, Botswana. J Int AIDS Soc. 2017 Nov;20(3):e25021. doi: 10.1002/jia2.25021.
citation: Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S, van Widenfelt E, Leidner J, McIntosh K, Mazhani L, Makhema J, Essex M, Shapiro R. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial. Lancet Glob Health. 2017 May;5(5):e491-e500. doi: 10.1016/S2214-109X(17)30143-2.
citation: Ajibola G, Zash R, Shapiro RL, Batlang O, Botebele K, Bennett K, Chilisa F, Widenfelt EV, Makhema J, Lockman S, Holmes LB, Powis KM. Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana. PLoS One. 2017 Mar 24;12(3):e0173800. doi: 10.1371/journal.pone.0173800. eCollection 2017.