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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04518228
• Other study ID #: IMPAACT 2026
• Secondary ID: 38609
• Status: Recruiting
• Start date: September 1, 2021
• Est. completion date: March 11, 2026

Study information

• Verified date: January 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum.

Description:

This study will evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum.

IMPAACT 2026 is a Phase IV observational clinical study. Participants are not assigned to the drugs under study, but are already receiving the drugs for clinical care by prescription of their clinical care providers. They are enrolled into study arms according to the drugs they are receiving through clinical care, and if on multiple drugs of interest, are able to enroll into multiple arms simultaneously. No ARVs or TB treatment drugs are supplied as part of this study. All drugs under study are 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 decides to prescribe a higher dose than the approved dose if the PK results for the approved dose indicate that drug exposure may be inadequate.

This study is 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 will open to accrual independently and will accrue independently over approximately 36 months from the first enrollment in each arm.

Participants in Component 1 will be followed up to 12 weeks after delivery for mothers and up to 24 weeks after birth for infants. Participants in Component 2 will be followed up to 5 weeks after delivery for mothers and infants. Participants in Components 3, 4, and 5 will be 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 325
• Est. completion date: March 11, 2026
• Est. primary completion date: March 11, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Component 1: Pregnant WLHIV receiving oral ARVs and no TB drugs, and their infants

• Mother is of legal age or otherwise able to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with site institutional review board (IRB)/ethics committee (EC) policies and procedures, and is willing and able to provide written informed consent for her own and her infant's participation in this study.

• Prior to study entry, HIV status confirmed as HIV infected per study protocol.

• At study entry, pregnant and in one of the following two enrollment windows based on best available obstetrical estimate of gestational age:

• Second trimester: gestational age of 20 0/7 to 26 6/7 weeks

• Third trimester: gestational age of 30 0/7 to 37 6/7 weeks

• At study entry, receiving at least one of the following oral ARV drugs or drug combinations, based on maternal report and available medical records:

• Arm 1.1: Bictegravir (BIC) 50 mg q.d.

• Arm 1.2: Doravirine (DOR) 100 mg q.d.

• Arm 1.3: Tenofovir alafenamide (TAF) - 10 mg q.d. boosted with cobicistat

• Arm 1.4: TAF 25 mg q.d. without boosting

• Arm 1.5: TAF 25 mg q.d. boosted with cobicistat or ritonavir

• At study entry, planning to continue the current ARV regimen through at least 12 weeks post-delivery, based on maternal report and available medical records.

• At study entry, has been receiving the drug or drug combination under study at the required dose for at least two weeks, based on maternal report and available medical records.

• At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within 20 0/7 - 26 6/7 weeks gestation (second trimester) or 30 0/7 to 37 6/7 weeks gestation (third trimester) and within 14 days of enrollment.

• At study entry, if receiving a generic formulation of the drug or drug combination under study, approval of the formulation per study protocol.

• At study entry, not receiving any TB drugs (for either prophylaxis or treatment), based on maternal report and available medical records.

Component 2: Pregnant WLHIV and HIV-uninfected women who received long-acting/extended release ARVs during pregnancy, and their infants

• If of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for her own and her infant's participation in this study.

• If not of legal age or otherwise unable to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Parent/guardian or other legally authorized representative of the mother and her infant is willing and able to provide written informed consent for the mother and her infant's study participation; in addition, when applicable, the mother is willing and able to provide written assent for her own and her infant's study participation.

• At study entry, intends to deliver at the study-affiliated clinic or hospital, based on maternal report.

• At study entry, gestational age of at least 24 0/7 weeks based on best available obstetrical estimate of gestational age, and not yet delivered.

• At study entry, has received at least one administration of the following, based on available medical records, during the current pregnancy:

• Arm 2.1: Long-acting injectable formulation of cabotegravir (CAB LA) (any dose)

Component 3: Pregnant WLHIV receiving ARVs with first-line TB treatment, and their infants

• Mother is of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures, and is willing and able to provide written informed consent for her own and her infant's participation in this study.

• Prior to study entry, HIV status confirmed as HIV infected per study protocol.

• At study entry, pregnant and in one of the following two enrollment windows, based on best available obstetrical estimate of gestational age:

• Second trimester: gestational age of 20 0/7 to 26 6/7 weeks

• Third trimester: gestational age of 30 0/7 to 37 6/7 weeks

• At study entry, receiving at least two of the following first-line TB treatment drugs under study AND at least one of the following ARV drugs or drug combinations under study, based on maternal report and available medical records:

• First-line TB treatment drugs:

• Isoniazid (INH) 4-6 mg/kg (max 300 mg) q.d.

• Rifampin (RIF) 8-12 mg/kg (max 600 mg) q.d.

• Rifabutin (RFB) 150-300 mg q.d.

• Ethambutol (EMB) 15-20 mg/kg q.d.

• Pyrazinamide (PZA) 20-30 mg/kg q.d.

• Moxifloxacin (MFX) 400 mg or 800mg q.d

• ARVs:

• Arm 3.1: Dolutegravir (DTG) 50 mg b.i.d. when combined with RIF or 50 mg q.d. if RIF is not part of the TB regimen

• Arm 3.2: Atazanavir/ritonavir (ATV/r) =300/100 mg q.d. or Darunavir/ritonavir (DRV/r) = 600/100 mg b.i.d.

• Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d.

• At study entry, has been receiving the drug combination under study at the required dose for at least two weeks based on maternal report and available medical records.

• At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within 20 0/7 - 26 6/7 weeks gestation (second trimester) or 30 0/7 to 37 6/7 weeks gestation (third trimester) and within 14 days of enrollment.

• At study entry, if receiving a generic ARV or TB formulation of the drug or drug combination under study, approval of the formulation per study protocol.

• At study entry, planning to continue the current ARV regimen through at least 8 weeks post-delivery, based on maternal report and available medical records.

Component 4 Inclusion Criteria: Pregnant WLHIV and HIV-uninfected women receiving second-line TB treatment, and their infants

• Mother is of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures, and is willing and able to provide written informed consent for her own and her infant's participation in this study.

• Prior to study entry, HIV status confirmed as HIV-infected or HIV-uninfected, per study protocol.

• At study entry, pregnant and in one of the following two enrollment windows based on best available obstetrical estimate of gestational age:

• Second trimester: gestational age of 20 0/7 to 26 6/7 weeks

• Third trimester: gestational age of 30 0/7 to 37 6/7 weeks

• At study entry, receiving at least one of the following second-line TB treatment drugs under study, based on maternal report and available medical records:

• Arm 4.1: 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 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

• At study entry, has been receiving the drugs under study at the required dose for at least two weeks, based on maternal report and available medical records.

• At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within 20 0/7 - 26 6/7 weeks gestation (second trimester) or 30 0/7 to 37 6/7 weeks gestation (third trimester) and within 14 days of enrollment.

• At study entry, if receiving a generic formulation of the drug(s) under study, approval of the formulation per study protocol.

Component 5: Postpartum WLHIV breastfeeding while receiving oral ARVs, and their infants

• Mother is of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures, and is willing and able to provide written informed consent for her own and her infant's participation in this study.

• Prior to study entry, HIV status confirmed as HIV infected, per study protocol.

• At study entry, within 5-9 days post-delivery (inclusive).

• At study entry, breastfeeding mother-infant pair intends to continue exclusive breastfeeding through at least 16 weeks post-delivery.

• At study entry, mother is receiving any of the following oral ARV drugs or drug combinations:

• Arm 5.1: Atazanavir/ritonavir (ATV/r)

• Arm 5.2: Darunavir/ritonavir (DRV/r)

• Arm 5.3: Lopinavir/ritonavir (LPV/r)

• At study entry, mother has been receiving the drug(s) or drug combination(s) under study at the required dose for at least two weeks, based on maternal report and available medical records.

• At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within the 5-9 days post-delivery PK sampling window.

• At study entry, mother is planning to continue the current ARV regimen through at least 16 weeks post-delivery, based on maternal report and available medical records.

• At study entry, if receiving a generic ARV formulation of the drug or drug combination under study, approval of the formulation per study protocol.

• At study entry, infant weighs at least 1000 grams, based on available medical records.

• At study entry, infant does not have any severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the site investigator.

Components 1-4 Exclusion Criteria:

• At study entry, mother has received within the past 14 days medicines known to interfere with absorption, metabolism, or clearance of the drug or drug combination under study (see study protocol) based on maternal report and available medical records.

• Note: RIF is permitted for mothers in Components 3 and 4 being evaluated for TB and ARV drug interactions.

• At study entry, has a clinical or laboratory finding or condition that, in the opinion of the site investigator, is likely to require a change of the ARV or TB drug under study during the period of study follow-up.

• Arms 1.3, 1.4 and 1.5 only: At study entry, mother has received TDF-based therapy within the past 6 months.

Component 5 Exclusion Criteria

• Mother is currently enrolled in Components 1, 2, 3, or 4.

• At study entry, the mother or infant has received within the past 14 days medicines known to interfere with absorption, metabolism, or clearance of the drug or drug combination under study based on maternal report and available medical records (see study protocol).

• At study entry, mother or infant has a clinical or laboratory finding or condition that, in the opinion of the site investigator, is likely to require a change of the drug under study during study follow-up.

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• Bictegravir (BIC)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Tenofovir alafenamide (TAF)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Cabotegravir (CAB)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Dolutegravir (DTG)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Atazanavir/ritonavir (ATV/r)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Darunavir/ritonavir (DRV/r)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Lopinavir/ritonavir (LPV/r)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Cobicistat
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• Ritonavir
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
• First-Line TB Treatment
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.
• Second-Line TB Treatment
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.
• Doravirine (DOR)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Locations

Country	Name	City	State
Botswana	Gaborone CRS (Site ID: 12701)	Gaborone	South-East District
Botswana	Molepolole CRS (Site ID: 12702)	Molepolole	Kweneng District
Brazil	SOM Federal University Minas Gerais Brazil NICHD CRS	Belo Horizonte
Brazil	Univ. of Sao Paulo Brazil NICHD CRS (Site ID: 5074)	Ribeirão Preto	São Paulo
Brazil	Hosp. Geral De Nova Igaucu Brazil NICHD CRS	Rio De Janeiro
Brazil	Hospital Federal dos Servidores do Estado NICHD CRS	Rio De Janeiro
India	Byramjee Jeejeebhoy Medical College (BJMC) CRS	Pune	Maharashtra
Kenya	Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS	Kericho
Malawi	Malawi CRS	Lilongwe
Puerto Rico	IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS	San Juan
South Africa	Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS	Cape Town
South Africa	Sizwe CRS	Johannesburg
South Africa	Wits RHI Shandukani Research	Johannesburg	Gauteng
South Africa	Famcru Crs	Tygerberg Hills
Tanzania	Kilimanjaro Christian Medical Centre (KCMC) (Site ID: 5118)	Moshi
Thailand	Siriraj Hospital, Mahidol University NICHD CRS	Bangkok	Bangkoknoi
Thailand	Chiangrai Prachanukroh Hospital NICHD CRS (Site ID: 5116)	Chiang Rai
Uganda	Baylor-Uganda CRS	Kampala
United States	Emory University School of Medicine NICHD CRS	Atlanta	Georgia
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	Johns Hopkins Univ. Baltimore NICHD CRS	Baltimore	Maryland
United States	Bronx-Lebanon Hospital Center NICHD CRS	Bronx	New York
United States	Jacobi Med. Ctr. Bronx NICHD CRS	Bronx	New York
United States	Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001)	Chicago	Illinois
United States	Rush University Cook County Hospital Chicago NICHD CRS	Chicago	Illinois
United States	South Florida CDTC Ft Lauderdale NICHD CRS	Fort Lauderdale	Florida
United States	Baylor College of Medicine/ Texas Children's Hospital NICHD CRS (Site ID: 5128)	Houston	Texas
United States	University of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	David Geffen School of Medicine at UCLA NICHD CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	St. Jude Children's Research Hospital CRS	Memphis	Tennessee
United States	Pediatric Perinatal HIV NICHD CRS	Miami	Florida
United States	University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program	San Diego	California
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
Zimbabwe	Harare Family Care CRS (Site ID: 31890)	Harare
Zimbabwe	Seke North CRS (Site ID: 30306)	Seke North	Chitungwiza
Zimbabwe	St Mary's CRS (Site ID: 30303)	St. Mary's	Chitungwiza

Sponsors (7)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Gilead Sciences, International Maternal Pediatric Adolescent AIDS Clinical Trials Group, Merck Sharp & Dohme LLC, National Institute of Mental Health (NIMH), ViiV Healthcare

Countries where clinical trial is conducted

United States,  Zimbabwe,  Botswana,  Brazil,  India,  Kenya,  Malawi,  Puerto Rico,  South Africa,  Tanzania,  Thailand,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of women who meet area under the curve (AUC) target in second trimester (2T)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at 2T (20 0/7 weeks to 26 6/7 weeks of pregnancy)
Primary	Number of women who meet area under the curve (AUC) target in third trimester (3T)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at 3T (30 0/7 weeks to 37 6/7 weeks of pregnancy)
Primary	Number of women who meet area under the curve (AUC) in postpartum (PP)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at PP (6 to 12 weeks after delivery)
Primary	Area under the curve (AUC) in second trimester (2T)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at 2T (20 0/7 weeks to 26 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) in third trimester (3T)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at 3T (30 0/7 weeks to 37 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) postpartum (PP)	For Arms 1.1, and 1.2: BIC, DOR only	Measured at PP (6 to 12 weeks after delivery)
Primary	Tenofovir-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) in second trimester (2T)	For Arms 1.3, 1.4, and 1.5 only	Measured at 2T (20 0/7 weeks to 26 6/7 weeks of pregnancy)
Primary	Tenofovir-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) in third trimester (3T)	For Arms 1.3, 1.4, and 1.5 only	Measured at 3T (30 0/7 weeks to 37 6/7 weeks of pregnancy)
Primary	Tenofovir-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) postpartum (PP)	For Arms 1.3, 1.4, and 1.5 only	Measured at PP (6 to 12 weeks after delivery)
Primary	Cord blood/maternal plasma concentration ratio at delivery	For Arm 2.1.: CAB only	Measured on Day 0
Primary	Infant washout half-life after delivery (if not breastfeeding)	For Arm 2.1: CAB only	Measured on Day 0
Primary	Maternal breast milk/maternal plasma concentration ratio (if breast feeding)	For Arm 2.1: CAB only	Measured at Day 0
Primary	Infant plasma concentration at breast milk PK visit (if breast feeding)	For Arm 2.1: CAB only	Measured through Week 5
Primary	Area under the curve (AUC) at second trimester (2T)	For Arms 3.1, 3.2 and 3.3 only	Measured at 2T (20 0/7 weeks to 26 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) at third trimester (3T)	For Arms 3.1, 3.2 and 3.3 only	Measured at 3T (30 0/7 weeks to 37 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) postpartum (PP)	For Arms 3.1, 3.2 and 3.3 only	Measured at PP (6 to 12 weeks after delivery)
Primary	Area under the curve (AUC) at second trimester (2T)	For Arm 4.1 only	Measured at 2T (20 0/7 weeks to 26 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) at third trimester (3T)	For Arm 4.1 only	Measured at 3T (30 0/7 weeks to 37 6/7 weeks of pregnancy)
Primary	Area under the curve (AUC) postpartum (PP)	For Arm 4.1 only	Measured at PP (6 to 12 weeks after delivery)
Primary	Maternal breast milk/maternal plasma concentration ratio	For Arms 5.1, 5.2, and 5.3 only	Measured through Week 24
Primary	Infant plasma concentration	For Arms 5.1, 5.2, and 5.3 only	Measured through Week 24
Secondary	Ratio of cord blood concentration to maternal blood concentration	For Components 1, 3 and 4, all Arms	Measured at Day 0
Secondary	Infant washout half-life of drug after birth (if the infant is not breastfeeding, and if the half-life is estimable)	For Components 1, 3 and 4, all Arms	Measured through Day 9
Secondary	Maternal breast milk/maternal plasma concentration ratio	For Components 3 and 4, if assessed	Measured through Week 24
Secondary	Infant plasma concentration	For Components 3 and 4, if assessed	Measured through Week 24
Secondary	Efavirenz, lopinavir, atazanavir, darunavir, dolutegravir, and/or raltegravir: AUC at second trimester (2T), third trimester (3T), and postpartum (PP)	For Component 4 only	Measured at Measured at 2T (20 0/7 to 26 6/7 weeks of pregnancy), 3T (30 0/7 to 37 6/7 weeks or pregnancy, and PP (2-8 weeks after delivery)
Secondary	Frequency of grade 3 or higher maternal adverse events	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	Measured through Week 24
Secondary	Frequency of grade 2 or higher infant adverse events	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	Measured through Week 24
Secondary	Frequency of maternal and infant serious adverse events	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	Measured through Week 24
Secondary	Frequency of grade 3 or higher maternal adverse events assessed as related to the drug under study	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	Measured through Week 24
Secondary	Frequency of grade 2 or higher infant adverse events assessed as related to the drug under study	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	Measured through Week 24
Secondary	Pregnancy outcome: occurrence of live birth versus fetal loss/stillbirth.		Measured on Day 0
Secondary	Gestational age at birth		Measured on Day 0
Secondary	Birth weight		Measured on Day 0
Secondary	Occurrence of congenital anomaly		Measured from Day 0 through Week 24 for Components 1, 3, 4 and 5; measured from Day 0 through Week 5 for Component 2
Secondary	Occurrence of mitochondrial disorder		Measured from Day 0 through Week 24 for Components 1, 3, 4 and 5; measured from Day 0 through Week 5 for Component 2
Secondary	Number of infants with confirmed positive HIV nucleic acid test result	Determined according to diagnosis per local standard of care	Measured from Day 0 through Week 24
Secondary	Maternal HIV-1 RNA		Measured at 2T (20 0/7 to 26 6/7 weeks of pregnancy), 3T (30 0/7 to 37 6/7 weeks or pregnancy, and PP (2-12 weeks after delivery)