NCT04518228

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 205 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: Female
• Age: —
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• HIV Infections
• Tuberculosis

Interventions

Type	Name	Description
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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	Cobicistat	Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
DRUG	Ritonavir	Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants
DRUG	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.
DRUG	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.
DRUG	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

Timeline

• Start date: 2021-09-01
• Primary completion: 2025-04-24
• Completion: 2025-07-10
• First posted: 2020-08-19
• Last updated: 2025-11-12

Locations

23 sites across 8 countries: United States, Brazil, India, Kenya, Puerto Rico, South Africa, Thailand, Uganda

Regulatory

• FDA-regulated drug study