Breastmilk transfer of cabotegravir and infant safety outcomes in mothers on cabotegravir for HIV prevention in Lilongwe, Malawi: A protocol for an observational pharmacokinetic study, CABMILK Study

Background: Long-acting injectable cabotegravir (CAB-LA) is highly effective for HIV pre-exposure prophylaxis (PrEP). However, lactating women have been underrepresented in pharmacokinetic and safety studies despite their elevated risk of HIV acquisition and potential postnatal transmission through breastfeeding. Data on cabotegravir transfer into breast milk and infant exposure remain limited. The Cabotegravir in Mother-Infant Pairs and Lactation Pharmacokinetics (CABMILK) study addresses this evidence gap to inform safe and equitable PrEP delivery within maternal and child health services in Malawi. Objectives: The primary objective is to quantify cabotegravir transfer into breast milk and estimate infant exposure following maternal use of CAB-LA for PrEP. Secondary objectives are to describe and contextualise infant safety outcomes, including growth, developmental status, and adverse events-among infants whose mothers receive CAB-LA, oral PrEP (tenofovir disoproxil fumarate/emtricitabine), or no PrEP, and to explore maternal factors associated with breast milk drug concentrations. Methods: CABMILK is an observational pharmacokinetic study nested within two ongoing CAB-LA implementation studies in Malawi. A total of 100 mother-infant pairs will be enrolled: 25 receiving CAB-LA, 25 receiving oral PrEP, and 50 PrEP-naïve. Serial maternal plasma and breast milk samples will be collected to quantify cabotegravir concentrations using validated LC-MS/MS assays and to estimate milk-to-plasma ratios and infant exposure. Infant safety monitoring will include clinical assessments, growth measurements, and developmental evaluation using the Caregiver Reported Early Development Index (CREDI) Short Form over 8 months of follow-up. Expected findings: This study will provide empirical data on cabotegravir transfer into breast milk, quantify infant exposure, and generate early comparative safety data. Conclusions: CABMILK will generate essential evidence to guide the safe implementation of CAB-LA among breastfeeding women and inform HIV prevention policy in high-burden settings.