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

Recruitment & Eligibility

Status: Recruiting

Sex: Female

Target Recruitment: 325

Inclusion Criteria

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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