Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum

This study evaluated the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum. IMPAACT 2026 was a Phase IV observational clinical study. Participants were not assigned to the drugs under study, but were already receiving the drugs for clinical care as prescribed by their clinical care providers. They were enrolled into study arms according to the drugs they were receiving through clinical care, and if on multiple drugs of interest, were able to enroll into multiple arms simultaneously. No ARVs or TB treatment drugs were supplied as part of this study. All drugs under study were provided by non-study sources. The study sponsor added this observational study to an existing investigational new drug (IND) number for off-label use in case the participant's clinical care provider decided to prescribe a higher dose than the approved dose if the PK results for the approved dose indicated that drug exposure may be inadequate. This study was comprised of five components which in turn are comprised of arms specific to each drug or drug combination being evaluated: * Component 1 (Arms 1.1, 1.2. 1.3. 1.4. and 1.5): Pregnant women living with HIV (WLHIV) receiving oral ARVs and no TB drugs, and their infants. * Component 2 (Arm 2.1): Pregnant WLHIV and HIV-uninfected women who received long-acting/extended release ARVs during pregnancy, and their infants. * Component 3 (Arms 3.1, 3.2, and 3.3): Pregnant WLHIV receiving ARVs and first-line TB treatment, and their infants. * Component 4 (Arm 4.1): Pregnant WLHIV and HIV-uninfected women receiving second-line TB treatment, and their infants. * Component 5 (Arms 5.1, 5.2. and 5.3): Postpartum WLHIV breastfeeding while receiving oral ARVs, and their infants. Each arm was to open to accrual independently and accrue independently over approximately 36 months from the first enrollment in each arm. Participants signed a single informed consent for the Component to which they enrolled, and they could only enroll into one component. Women receiving more than one drug under study in a single Component (and their infants) were automatically enrolled into all relevant open arms within that component, based on the drugs under study they were receiving at study entry. There were no changes in arm during the study; a study inclusion criterion was that participants expected to remain on the same treatment regimen until study completion. Participants in Component 1 were followed up to 12 weeks after delivery for mothers and up to 24 weeks after birth for infants. Participants in Component 2 were to be followed up to 5 weeks after delivery for mothers and infants. Participants in Components 3, 4, and 5 were followed up to 24 weeks after delivery for mothers and infants. Study visits may include: * Component 1: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 6-12 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth. * Component 2: Maternal clinical and laboratory evaluations and PK sampling at delivery. Infant clinical evaluations and washout PK sampling at birth, 5-9 days, and 12-16 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 12-16 days, and 3-5 weeks after delivery. * Component 3: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 2-8 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery. * Component 4: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 2-8 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery. * Component 5: Maternal and infant clinical evaluations and breast milk transfer PK sampling at 5-9 days, 2-12 weeks, and 16-24 weeks after delivery. Component 2 (Arm 2.1) never opened for enrollment because investigations of the PK and safety of long-acting injectable cabotegravir in pregnancy were to be conducted in a separate study. Arms 1.1 and 1.4 reached their enrollment targets and were closed to accrual. Arms 1.3 and 5.1 were closed to accrual per the decision of the Core Protocol Team because enrollment had slowed substantially and enough participants had been enrolled to proceed with data analysis and publication. Arms 1.5, 3.2,3.3, 5.2, and 5.3 did not enroll any participants and were closed to accrual per the decision of the Core Protocol Team, because enrollment of enough participants to result in a publication was not anticipated. The study was closed to accrual on March 5, 2025 at the recommendation of the IMPAACT Study Monitoring Committee (SMC). Prior to closure, 3 arms had open to accrual status: Arms 1.2, 3.1, and 4.1. The SMC suggested that the study objectives for Arm 3.1 could be achieved with the sample size at the time of closure and that the study objectives for Arms 1.2 and 4.1 could not be met within a reasonable timeframe.