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

NCT04518228 | Completed DMC FDA Drug

• 2 other identifiers: IMPAACT 202638609
• Study Type: observational
• Target: 205
• Locations: 8 countries
• Sites: 23

Brief 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.

Conditions

HIV Infections; Tuberculosis

Outcome Measures

Primary Outcomes (21)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• Cord blood/maternal plasma concentration ratio at delivery

  For Arm 2.1.: CAB only

  Measured on Day 0

• Infant washout half-life after delivery (if not breastfeeding)

  For Arm 2.1: CAB only

  Measured on Day 0

• Maternal breast milk/maternal plasma concentration ratio (if breast feeding)

  For Arm 2.1: CAB only

  Measured at Day 0

• Infant plasma concentration at breast milk PK visit (if breast feeding)

  For Arm 2.1: CAB only

  Measured through Week 5

• 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)

• 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)

• 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)

• 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)

• 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)

• Area under the curve (AUC) postpartum (PP)

  For Arm 4.1 only

  Measured at PP (6 to 12 weeks after delivery)

• Maternal breast milk/maternal plasma concentration ratio

  For Arms 5.1, 5.2, and 5.3 only

  Measured through Week 24

• Infant plasma concentration

  For Arms 5.1, 5.2, and 5.3 only

  Measured through Week 24

Secondary Outcomes (17)

• Ratio of cord blood concentration to maternal blood concentration

  Measured at Day 0

• Infant washout half-life of drug after birth (if the infant is not breastfeeding, and if the half-life is estimable)

  Measured through Day 9

• Maternal breast milk/maternal plasma concentration ratio

  Measured through Week 24

• Infant plasma concentration

  Measured through Week 24

• Efavirenz, lopinavir, atazanavir, darunavir, dolutegravir, and/or raltegravir: AUC at second trimester (2T), third trimester (3T), and postpartum (PP)

  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)

Study Arms (13)

Component 1: Arm 1.1: Bictegravir (BIC) 50 mg q.d.

Women ≥ 20 weeks gestation not receiving TB drugs and receiving bictegravir (BIC) 50 mg once daily (q.d.), and their infants

Drug: Bictegravir (BIC)

Component 1: Arm 1.2: Doravirine (DOR) 100 mg q.d.

Women ≥ 20 weeks gestation not receiving TB drugs and receiving doravirine (DOR) 100 mg q.d., and their infants

Drug: Doravirine (DOR)

Component 1: Arm 1.3: Tenofovir alafenamide (TAF) 10 mg q.d.

Women ≥ 20 weeks gestation not receiving TB drugs and receiving tenofovir alafenamide (TAF) 10 mg q.d. boosted with cobicistat, and their infants

Drug: Tenofovir alafenamide (TAF); Drug: Cobicistat

Component 1: Arm 1.4: TAF 25 mg q.d. without boosting

Women ≥ 20 weeks gestation not receiving TB drugs and receiving TAF 25 mg q.d. without boosting, and their infants

Drug: Tenofovir alafenamide (TAF)

Component 1: Arm 1.5: TAF 25 mg q.d. with boosting

Women ≥ 20 weeks gestation not receiving TB drugs and receiving TAF 25 mg q.d. boosted with cobicistat or ritonavir, and their infants

Drug: Tenofovir alafenamide (TAF); Drug: Cobicistat; Drug: Ritonavir

Component 2: Arm 2.1: CAB LA

Women ≥ 24 weeks gestation who received at least one dose of long-acting injectable formulation of cabotegravir (CAB LA) any dose during pregnancy, and their infants

Drug: Cabotegravir (CAB)

Component 3: Arm 3.1: Dolutegravir (DTG) 50 mg

Women ≥ 20 weeks gestation 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), moxifloxacin (MFX), and receiving dolutegravir (DTG) 50 mg twice daily (b.i.d.) when combined with RIF or 50 mg q.d. if RIF is not part of the TB regimen, and their infants

Drug: Dolutegravir (DTG); Drug: First-Line TB Treatment

Component 3: Arm 3.2: ATV/r or DRV/r

Women ≥ 20 weeks gestation 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), moxifloxacin (MFX), and receiving atazanavir/ritonavir (ATV/r) ≥ 300/100 mg q.d. or darunavir/ritonavir (DRV/r) ≥ 600/100 mg b.i.d., and their infants

Drug: Atazanavir/ritonavir (ATV/r); Drug: Darunavir/ritonavir (DRV/r); Drug: First-Line TB Treatment

Component 3: Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg

Women ≥ 20 weeks gestation 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), moxifloxacin (MFX), and receiving lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d., and their infants

Drug: Lopinavir/ritonavir (LPV/r); Drug: First-Line TB Treatment

Component 4: Arm 4.1: Second-line TB treatment drugs

Women ≥ 20 weeks gestation receiving at least one of the following second-line TB treatment drugs, and their infants: * 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

Drug: Second-Line TB Treatment

Component 5: Arm 5.1: ATV/r

Women post-delivery receiving ATV/r, and their infants

Drug: Atazanavir/ritonavir (ATV/r)

Component 5: Arm 5.2: DRV/r

Women post-delivery receiving DRV/r, and their infants

Drug: Darunavir/ritonavir (DRV/r)

Component 5: Arm 5.3: LPV/r

Women post-delivery receiving LPV/r, and their infants

Drug: Lopinavir/ritonavir (LPV/r)

Interventions

Bictegravir (BIC) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 1: Arm 1.1: Bictegravir (BIC) 50 mg q.d.

Tenofovir alafenamide (TAF) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 1: Arm 1.3: Tenofovir alafenamide (TAF) 10 mg q.d.; Component 1: Arm 1.4: TAF 25 mg q.d. without boosting; Component 1: Arm 1.5: TAF 25 mg q.d. with boosting

Cabotegravir (CAB) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 2: Arm 2.1: CAB LA

Dolutegravir (DTG) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 3: Arm 3.1: Dolutegravir (DTG) 50 mg

Atazanavir/ritonavir (ATV/r) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 3: Arm 3.2: ATV/r or DRV/r; Component 5: Arm 5.1: ATV/r

Darunavir/ritonavir (DRV/r) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 3: Arm 3.2: ATV/r or DRV/r; Component 5: Arm 5.2: DRV/r

Lopinavir/ritonavir (LPV/r) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 3: Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg; Component 5: Arm 5.3: LPV/r

Cobicistat DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 1: Arm 1.3: Tenofovir alafenamide (TAF) 10 mg q.d.; Component 1: Arm 1.5: TAF 25 mg q.d. with boosting

Ritonavir DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 1: Arm 1.5: TAF 25 mg q.d. with boosting

First-Line TB Treatment DRUG

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.

Component 3: Arm 3.1: Dolutegravir (DTG) 50 mg; Component 3: Arm 3.2: ATV/r or DRV/r; Component 3: Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg

Second-Line TB Treatment DRUG

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.

Component 4: Arm 4.1: Second-line TB treatment drugs

Doravirine (DOR) DRUG

Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Component 1: Arm 1.2: Doravirine (DOR) 100 mg q.d.

Eligibility Criteria

• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant and postpartum women living with and without HIV (WLHIV and HIV-uninfected women) receiving ARV and/or TB drugs under study, and their infants.

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

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

Study Sites (23)

Usc La Nichd Crs

Los Angeles, California, 90033, United States

Location

David Geffen School of Medicine at UCLA NICHD CRS

Los Angeles, California, 90095-1752, United States

Location

University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program

San Diego, California, 92103, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

University of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

Pediatric Perinatal HIV NICHD CRS

Miami, Florida, 33136, United States

Location

Emory University School of Medicine NICHD CRS

Atlanta, Georgia, 30322, United States

Location

Rush University Cook County Hospital Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001)

Chicago, Illinois, 60614, United States

Location

Johns Hopkins Univ. Baltimore NICHD CRS

Baltimore, Maryland, 21287, United States

Location

Bronx-Lebanon Hospital Center NICHD CRS

The Bronx, New York, 10457, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, 20221-903, Brazil

Location

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, 26030, Brazil

Location

Byramjee Jeejeebhoy Medical College (BJMC) CRS

Pune, Maharashtra, 411001, India

Location

Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS

Kericho, 20200, Kenya

Location

IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS

San Juan, 00935, Puerto Rico

Location

Wits RHI Shandukani Research

Johannesburg, Gauteng, 2001, South Africa

Location

Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS

Cape Town, 7505, South Africa

Location

Famcru Crs

Tygerberg Hills, 7505, South Africa

Location

Siriraj Hospital, Mahidol University NICHD CRS

Bangkok, Bangkoknoi, 10700, Thailand

Location

Baylor-Uganda CRS

Kampala, Uganda

Location

Related Publications (1)

• Powis KM, Pinilla M, McMorrow F, Stek A, Brooks KM, Shapiro DE, Knowles K, Eke AC, Greene E, Agwu A, Topete L, Browning R, Chakhtoura N, Arora P, Huang X, Best BM, Mirochnick M, Momper JD; IMPAACT 2026 Protocol Team. Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants. J Acquir Immune Defic Syndr. 2025 Mar 1;98(3):300-307. doi: 10.1097/QAI.0000000000003571.

  PMID: 39813286 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

bictegravir; tenofovir alafenamide; cabotegravir; dolutegravir; atazanavir, ritonavir drug combination; Darunavir; Ritonavir; Lopinavir; Cobicistat; doravirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Pyrimidinones; Pyrimidines

Study Officials

• Mark Mirochnick, MD

  Boston University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: August 19, 2020
• Study Start: September 1, 2021
• Primary Completion: April 24, 2025
• Study Completion: July 10, 2025
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? * To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data

Locations

KE (1); TH (1); US (13); PR (1); ZA (3); IN (1); UG (1); BR (2)