CAP016 was an open-label trial conducted at a single hospital-based research site in Durban. Eligible pregnant adults at 14-28 weeks’ gestation at time of enrollment were assigned to either immediate PrEP initiation during pregnancy or deferred PrEP initiation at breastfeeding cessation. Enrollment started in September 2017 but was stopped in December 2019 when South Africa’s PrEP guidelines expanded to include pregnant people in the national roll-out. 540 women were ultimately enrolled (271 randomized to immediate PrEP and 269 to deferred PrEP). Median timing for PrEP start in the ‘immediate initiation’ group was 19 weeks’ gestation, with median time on study from randomization to delivery of 19.7 weeks. Mean calculated adherence was 87% at 4 weeks, 93% at 8 weeks, 94% at 12 weeks, and 95% at 16 weeks after PrEP initiation—nausea and vomiting in the first month (11%) as well as headache (14%) were reported as reasons for missed doses. Immediate PrEP initiation was not associated with preterm birth or small for gestational age birth. Investigators were unable to determine non-inferiority for less frequent outcomes (e.g., very preterm birth, low birthweight, very low birthweight, and stillbirth). No renal function abnormalities were observed. Four maternal HIV seroconversions were observed: 3 in the immediate PrEP group between 27 weeks and 35 weeks gestation, and 1 in the deferred PrEP group at 32 weeks gestation. All four neonates tested negative for HIV within 14 days of birth.