The purpose of this study was to evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered 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.
Study Type
OBSERVATIONAL
Enrollment
205
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
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Number of Women Who Meet Area Under the Curve (AUC) Target in Plasma (Component 1)
A target AUC was derived for each drug as the 10th percentile for the non-pregnant population based on historical control data. The target AUC is 58.7 mg\*h/L for Arm 1.1 and 10.0 mg\*h/L for Arm 1.2. Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. McNemar's test was not conducted for Arm 1.2 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
Median Maternal AUC in Plasma (Component 1)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. Wilcoxon signed-rank test was not conducted for Arm 1.2 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
Median Maternal Tenofovir-diphosphate (TFV-DP) Concentrations in Dried Blood Spots (DBS) (Component 1)
TFV-DP intracellular concentrations in DBS samples. Concentrations obtained from two 7 mm punches.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose.
Median Maternal Tenofovir-diphosphate (TFV-DP) Concentrations in Peripheral Blood Mononuclear Cells (PBMCs ) (Component 1)
TFV-DP intracellular concentrations in PBMC samples.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose and at 3 and 24 hours post-dose.
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Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Participants will be receiving first-line TB treatment with at least two of the following TB treatment drugs: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamide (PZA), or moxifloxacin (MFX). Drugs will be administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants.
Participants will be receiving second-line TB treatment with at least one of the following second-line TB treatment drugs: * Levofloxacin (LFX) 750mg - 1000mg q.d. * Clofazimine (CFZ) 100mg q.d. * Linezolid (LZD) 300mg - 600mg q.d. * Bedaquiline (BDQ) 200mg three times per week (t.i.w.) * Delamanid (DLM) 100mg b.i.d. * Moxifloxacin (MFX) 400mg or 800mg q.d., and at least one other second-line TB treatment drug under study Drugs will be administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants.
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
Los Angeles, California, United States
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, United States
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
San Diego, California, United States
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States
South Florida CDTC Ft Lauderdale NICHD CRS
Fort Lauderdale, Florida, United States
University of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States
Pediatric Perinatal HIV NICHD CRS
Miami, Florida, United States
Emory University School of Medicine NICHD CRS
Atlanta, Georgia, United States
Rush University Cook County Hospital Chicago NICHD CRS
Chicago, Illinois, United States
Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001)
Chicago, Illinois, United States
...and 13 more locations
Median Maternal Isoniazid (INH) AUC in Plasma (Component 3)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Rifampin (RIF) AUC in Plasma (Component 3)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Ethambutol (EMB) AUC in Plasma (Component 3)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Pyrazinamide (PZA) AUC in Plasma (Component 3)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Comparison of Antepartum vs. Postpartum was not done due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Dolutegravir (DTG) AUC in Plasma (Component 3)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. The data of the P1026s arm was not reported since it's not one of the arms in this study.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Bedqauiline (BDQ) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Clofazimine (CFZ) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Delamanid (DLM) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Levofloxacin (LFX) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Linezolid (LZD) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Atazanavir (ATV) Breast Milk/Maternal Plasma Concentration Ratio (Component 5)
Breast milk and maternal plasma concentrations were collected at study visits and compared as a ratio. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Only measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol.
Time frame: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Median Maternal Ritonavir (RTV) Breast Milk/Maternal Plasma Concentration Ratio (Component 5)
Breast milk and maternal plasma concentrations were collected at study visits and compared as a ratio. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Only measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol.
Time frame: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Infant Atazanvir (ATV) Plasma Concentration (Component 5)
Only measured for infants who met the breast milk transfer PK sampling requirements outlined in the protocol. The lower limit of quantitation (LLoQ) was 23.4 ng/mL for ATV.
Time frame: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life
Infant Ritonavir (RTV) Plasma Concentration (Component 5)
Only measured for infants who met the breast milk transfer PK sampling requirements outlined in the protocol. The lower limit of quantitation (LLoQ) was 9.8 ng/mL for RTV.
Time frame: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 1, Arms 1.1 and 1.2)
Cord blood and maternal blood concentrations were collected and measured for the drug(s) under study at delivery and compared as a ratio.
Time frame: Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 1, Arms 1.3 and 1.4)
Cord blood and maternal blood concentrations were collected and measured for the drug(s) under study at delivery and compared as a ratio. There are four analytes for Arms 1.3 and 1.4: tenofovir alafenamide fumarate (TAF) in plasma, tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS), TFV-DP in peripheral blood mononuclear cells (PBMCs), and tenofovir (TFV) in plasma. For Arm 1.3 TAF in plasma, all values were below the lower level of quantitation.
Time frame: Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 3)
Cord blood and maternal blood concentrations were collected and measured for the drugs under study at delivery and compared as a ratio. The analytes for Arm 3.1 were: isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), and dolutegravir (DTG).
Time frame: Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 4)
Cord blood and maternal blood concentrations were collected and measured for the drugs under study at delivery and compared as a ratio. The analytes for Arm 4.1 were: bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), levofloxacin (LFX), and linezolid (LZD).
Time frame: Measured at time of delivery with single cord blood and single maternal blood sample.
Median Infant Washout Half-life of Drug After Birth (Component 1)
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations. The analyte of Arm 1.4 is tenofovir in plasma.
Time frame: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant Washout Half-life of Drug After Birth (Component 3)
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations. The analytes for Arm 3.1 were: isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), and dolutegravir (DTG).
Time frame: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant Washout Half-life of Drug After Birth (Component 4)
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations where it was possible to calculate. The analytes for Arm 4.1 were: bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), levofloxacin (LFX), and linezolid (LZD).
Time frame: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Maternal Breast Milk/Maternal Plasma Concentration Ratio (Components 3 and 4)
Breast milk and maternal plasma concentrations were collected at study visits to be compared as a ratio, measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Per the protocol, breast milk transfer sampling was not to be performed for Arm 3.1. For Arm 4.1, samples were collected but not run and have yet to be analyzed. The anticipated reporting date is April 2027.
Time frame: Measured at 2-8 weeks postpartum (and 5-9 days and 16-24 weeks post-delivery if the requirements for breast milk transfer PK sampling are met)
Infant Plasma Concentration (Component 3)
Plasma concentrations as part of breast milk transfer sampling. Per the protocol, breast milk transfer sampling was not to be performed for Arm 3.1.
Time frame: Measured through Week 24
Median Infant Bedaquiline (BDQ) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Clofazimine (CFZ) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Delamanid (DLM) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Levofloxacin (LFX) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Linezolid (LZD) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Dolutegravir (DTG) Plasma Concentration (Component 4)
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Time frame: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Maternal Efavirenz (EFV) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Lopinavir (LPV) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Median Atazanavir (ATV) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Darunavir (DRV) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Dolutegravir (DTG) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Raltegravir (RAL) AUC in Plasma (Component 4)
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Time frame: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Number of Participants With Grade 3 or Higher Maternal Adverse Events
Maternal Grade 3 or higher adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Time frame: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Grade 2 or Higher Infant Adverse Events
Infant Grade 2 or higher adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Time frame: Measured from entry through Week 24
Number of Participants With Maternal Serious Adverse Events
Maternal serious adverse events which were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Time frame: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Infant Serious Adverse Events
Infant serious adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Time frame: Measured from entry through Week 24
Number of Participants With Grade 3 or Higher Maternal Adverse Events Assessed as Related to the Drug Under Study
Maternal Grade 3 or higher adverse events assessed as related to the drug under study. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Time frame: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Grade 2 or Higher Infant Adverse Events Assessed as Related to the Drug Under Study
Infant Grade 2 or higher adverse events assessed as related to the drug under study. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Time frame: Measured from entry through Week 24
Pregnancy Outcome
Outcome of pregnancy categorized as live birth, stillbirth, spontaneous abortion, and etc.
Time frame: Measured on maternal delivery date/infant Day 0
Median Gestational Age at Birth
Infant gestational age at birth (weeks)
Time frame: Measured on Day 0 (0-3 days)
Median Infant Birth Weight
Infant birth weight (grams)
Time frame: Measured on Day 0 (0-3 days)
Occurrence of Congenital Anomaly or Mitochondrial Disorder
Presence of any congenital anomaly or mitochondrial disorder identified in infants.
Time frame: Measured from Day 0 through Week 24 for Components 1, 3, 4 and 5; measured from Day 0 through Week 5 for Component 2
Infant HIV Status
Infant HIV status which is determined according to diagnosis per local standard of care
Time frame: Measured from Day 0 through Week 24
Maternal HIV-1 RNA
Plasma HIV-1 RNA levels in the mothers as in categories. The highest value of the lower limits of quantitation (LLoQ) for each arm was used for categorizations. The LLoQs are: Arm 1.1 - 40 copies/mL, Arm 1.2 - 20 copies/mL, Arm 1.3 and Arm 1.4 - 200 copies/mL, Arm 3.1 - 40 copies/mL, and Arm 4.1 - 50 copies/mL.
Time frame: Measured in 2nd Trimester,(2T, 20 0/7 to 26 6/7 weeks of pregnancy), 3rd Trimester (3T, 30 0/7 to 37 6/7 weeks of pregnancy), delivery, and PP (2-8 weeks or 6-12 weeks after delivery, depending on study arm)