Study participants were enrolled in two cohorts.
* Cohort 1 enrolled mother-infant pairs in which the infant was expected to be ≥2000 grams at birth (i.e. full term) at time of enrollment and the mother was living with HIV and received RAL 400 mg twice daily for at least 2 weeks prior to delivery and continued to receive antiretroviral (ARV) drugs during labor.
* Cohort 2 enrolled mother-infant pairs in which the infant was expected to be ≤2500 grams at birth \[i.e. low birth weight (LBW)\] at time of enrollment and the mother was living with HIV and received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery.
Cohorts 1 and 2 provided pharmacokinetics and safety data of in utero and intrapartum exposure to maternal RAL in full-term and LBW infants, respectively. Also, the study data were pooled with data from IMPAACT P1066 (NCT00485264) (Cohorts IV and V) and P1026s (NCT00042289) to determine the starting RAL dosing regimen for full-term and LBW infants in IMPAACT P1110 (NCT01780831).
The study initially opened accrual to Cohort 1 under protocol Version 1.0. Upon completion of accrual and follow-up of Cohort 1, the protocol was amended and accrual to and follow-up of Cohort 2 was under protocol Version 2.0.
No study-specific treatment was given to the participants during this study. The women (mothers) received RAL for clinical indications outside of the study. Infants received standard of care ARV therapy for prophylaxis of perinatal transmission of HIV as prescribed by their primary care physicians.
Cohort 1 mother-infant pairs were enrolled prior to delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth through 20 weeks after birth. If infant was eligible for PK sampling (see "Eligibility" section), blood samples were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth. Protocol defined infant safety evaluations were at birth, and at 8-14 hours, 30-36 hours, 1 week and 20 weeks after birth.
Cohort 2 mother-infant pairs were enrolled prior to delivery or within 48 hours after delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth/entry through 6 weeks after birth. If infant was eligible for PK sampling, blood samples were collected at 1-6, 12-24, 36-48, 72-84, and 108-132 hours and 7-14 days after birth. Protocol defined infant safety evaluations were at entry/birth, and at 36-48 hours, 72-84 hours, 1 week and 6 weeks after birth.
For both cohorts, all infants regardless of whether they were eligible for PK sampling were included in the safety analyses. Infant safety data included adverse birth outcomes, signs/symptoms, diagnoses and chemistry/hematology test results. Protocol required chemistry tests were AST, ALT, serum creatinine, total bilirubin and direct bilirubin. Protocol required hematology tests were CBC with differential and platelet count. Also included in the safety data were additional laboratory events done outside of the study but considered by the site as relevant information.
For both cohorts, maternal blood and cord blood for RAL concentration testing were collected at delivery when specimen collection was possible. The optional genotypic testing (i.e. testing was done only if the mother consented) was limited to infants who were eligible for PK sampling. Information obtained about the effect of UGT1A1 polymorphisms on the PK of RAL was thought to provide a better understanding of the effect of genetics on the metabolism of RAL in neonates.
