Linking HIV Prevention and Postpartum Care: Safety, Efficacy and Feasibility of Cabotegravir-LA PrEP in a High-Risk Breastfeeding Population in Botswana (Tshireletso Study)

Status: Ongoing

Primary Objectives

Specific Aim 1: To evaluate the uptake, adherence, implementation metrics, acceptability and effectiveness of a CAB-LA PrEP program for women at high risk of HIV enrolled immediately post-partum, with follow up co-located with routine postpartum/pediatric care whenever feasible=

Specific Aim 2: To evaluate the safety of CAB-LA PrEP in postpartum women and their breastfed infants

Specific Aim 3: To evaluate the pharmacokinetics of CAB-LA PrEP in postpartum women and their breastfed infants

Secondary Objectives

To describe maternal morbidity and mortality through 24 months and compare with existing post-partum cohorts enrolled in studies in Botswana that did not receive CAB-LA
To describe infant morbidity and mortality through 24 months and compare with existing post-partum cohorts enrolled in studies in Botswana that did not receive CAB-LA
To evaluate different HIV testing strategies for determination of breakthrough infections and development of integrase inhibitor (INSTI) resistance
To evaluate HIV drug resistance and health outcomes in women and infants who acquire HIV during the study
To describe pregnancy and birth outcomes among participants who become pregnant while taking CAB-LA PrEP
To evaluate HIV risk self evaluation as a predictor of incident HIV,PrEP adherence and acceptability
To perform a mixed methods survey to better understand reasons for declining CAB-LA PrEP
To perform a mixed methods survey to better understand participant preferences for HIV prevention during periods without CAB-LA coverage, including missed injections and during the pharmacologic tail
To investigate hair levels of CAB in mothers on CAB-based PrEP and their breastfeeding infants as a metric of maternal and infant exposure.

Study Design:

This is a hybrid implementation/safety study of long-acting cabotegravir (CAB-LA) as pre-exposure prophylaxis (PrEP) to prevent HIV infection in a post-partum cohort in Botswana where breastfeeding is common. We will enroll 500 women at high risk for HIV while they are admitted to the postpartum maternity ward after delivery at up to 4 government-run health care facilities in Botswana and follow them for 24 months. The first CAB-LA injection will occur within 14 days of delivery and generally before discharge from the maternity ward. Follow up injections at 1 month, and then every two months, administered at clinics where the women and their infants receive routine care or at research study sites. We will measure uptake, adherence, and implementation metrics using a mixed methods approach. We will also measure HIV incidence and safety outcomes, including postpartum depression, weight gain, and infant growth. Pharmacokinetics of CAB-LA in lactation (women, infants and breastmilk) will be evaluated in 30 mother-infant pairs enrolled in the main trial.

Study Population and Size: