BackgroundBreastfeeding offers significant health benefits, and guidance for women with HIV increasingly emphasizes individualized, informed infant-feeding decisions. Breastmilk antiretroviral transfer and safety data are needed to inform shared decision-making discussions across all settings.MethodsBreastmilk transfer of ritonavir (RTV)-boosted atazanavir (ATV) was evaluated in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2026 study. Fourteen breastfeeding women with HIV receiving RTV boosted ATV 100/300 mg daily, as part of a multi-drug regimen, and their infants were enrolled in Kenya, Uganda, and South Africa between 5 and 9 days postpartum and followed through age 16–24 weeks. Paired maternal plasma, breastmilk, and infant plasma samples were collected at each visit. Concentrations were measured using validated LC-MS/MS methods. Relative infant dose (RID) was estimated assuming an infant milk intake of 150 mL/kg/day. Safety outcomes were prospectively assessed.ResultsAll 14 women reported exclusive breastfeeding. Median maternal plasma and breastmilk concentrations were 1,410 ng/mL and 432 ng/mL for ATV, and 217 ng/mL and 13.6 ng/mL for RTV, respectively. Median breastmilk-to-plasma ratios were 0.253 (ATV) and 0.081 (RTV). RID values were 1.27% (maximum 6.43%) for ATV and 0.12% (maximum 1.10%) for RTV. Infant plasma concentrations were below the lower limit of quantitation (ATV 23.4 ng/mL; RTV 9.8 ng/mL) in all 42 samples. No maternal adverse events occurred; three infants experienced unrelated grade 2 events.ConclusionsIn this cohort, ATV and RTV were detectable in maternal plasma and breastmilk but not in infant plasma, with low RID estimates and a favorable safety profile.