Study to Improve Survival Among HIV-Exposed Infants in Botswana

Conditions

HIV Infections, Neutropenia, Anemia

Keywords

HIV, Trimethoprim-Sulfamethoxazole Combination, Breast Feeding, Infant Mortality, Morbidity, Botswana, Africa, Infectious disease transmission, vertical, adverse drug event

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.

Thivalapill N, Lockman S, Powis K, Zash R, Leidner J, Ajibola G, Mmalane M, Makhema J, Shapiro RL.

2021-10-171 citations

10.1186/s12874-021-01343-5

Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial.

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.

2017-05-0137 citations

10.1016/s2214-109x(17)30143-2

Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana

Gbolahan Ajibola, Rebecca Zash, Roger Shapiro, Oganne Batlang, Kerapetse Botebele et al. (12 authors)

PLoS ONE2017-03-248 citations

10.1371/journal.pone.0173800

Malaria burden in a birth cohort of HIV-exposed uninfected Ugandan infants living in a high malaria transmission setting.

Kakuru A, Natureeba P, Muhindo MK, Clark TD, Havlir DV, Cohan D, Dorsey G, Kamya MR, Ruel T.

2016-10-182 citations

10.1186/s12936-016-1568-z

Papers published before 2008-02-04 may not appear yet. Historical indexing is in progress.

Interventions

DRUGcotrimoxazole prophylaxis

100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months

DRUGcotrimoxazole placebo

100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months

BEHAVIORALexclusive breastfeeding until 6 months of age

Breastfeeding for 6 months, followed by formula feeding for 6 month. Breastfeeding infants will be prophylaxed with maternal highly active antiretroviral therapy (HAART) (if available) or with infant nevirapine.

BEHAVIORALbreastfeeding for 12 months

Breastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine.

Study design

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
Safety of CTX prophylaxis	18 months	Secondary outcome measures will evaluate the safety of CTX prophylaxis through 18 months
Morbidity and mortality	18 months of age	Secondary outcome measures will evaluate morbidity and mortality to 18 months.

Countries

Botswana

Outcome results

None listed