Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy

Completed

• Conditions: HIV Infections
• Interventions: Drug: darunavir/ritonavir dosage #1; Drug: TAF w/cobicistat; Drug: TAF w/cobicistat or ritonavir; Drug: tenofovir alafenamide fumarate (TAF); Drug: elvitegravir/cobicistat; Drug: darunavir/cobicistat; Drug: atazanavir/cobicistat; Drug: lopinavir/ritonavir dosage #1; Drug: atazanavir/ritonavir/tenofovir dosage #1; Drug: lopinavir/ritonavir dosage #2; Drug: indinavir/ritonavir dosage #1; Drug: fosamprenavir/ritonavir; Drug: atazanavir/ritonavir dosage #1; Drug: didanosine delayed release (Videx® EC); Drug: emtricitabine; Drug: nelfinavir dosage #1; Drug: tipranavir/ritonavir; Drug: etravirine; Drug: darunavir/ritonavir dosage #4; Drug: indinavir/ritonavir dosage #2; Drug: rilpivirine; Drug: ethambutol; Drug: efavirenz; Drug: raltegravir; Drug: dolutegravir; Drug: kanamycin; Drug: nevirapine; Drug: amprenavir; Drug: abacavir; Drug: tenofovir; Drug: maraviroc; Drug: nelfinavir dosage #2; Drug: darunavir/ritonavir dosage #2; Drug: lopinavir/ritonavir dosage #3; Drug: lopinavir/ritonavir dosage #4; Drug: tenofovir/atazanavir/ritonavir dosage #2; Drug: atazanavir/ritonavir dosage #2; Drug: rifampicin; Drug: amikacin; Drug: etonogestrel implant; Drug: darunavir/ritonavir dosage #3; Drug: capreomycin; Drug: ethinyl estradiol; Drug: isoniazid; Drug: moxifloxacin; Drug: levoflaxacin; Drug: pyrazinamide; Drug: ofloxacin; Drug: ethionamide/prothionamide; Drug: terizidone/cycloserine; Drug: para-aminosalicylic acid (PAS); Drug: high dose INH; Drug: bedaquiline; Drug: clofazamine; Drug: delamanid; Drug: linezolid; Drug: pretomanid

• Registration Number: NCT00042289
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs were evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.

Detailed Description

Pregnant women experience unique physiological changes that may result in clinically significant alterations in drug PKs. Unfortunately, there have been few clinical trials to study the PKs of ARV, TB, and hormonal contraceptive drugs in pregnant women. The development of appropriate dosing regimens for the HIV-infected pregnant woman is critical to the health of both mother and fetus. Overdosing may lead to maternal adverse events and increased risk of fetal toxicity, while underdosing may lead to inadequate virologic control, increased risk of developing drug resistance mutations, and a higher rate of perinatal HIV transmission. This study evaluated the PKs of ARVs used during pregnancy; the PKs of TB drugs used during pregnancy, both in women who are HIV-positive and also taking ARVs and in women who are HIV-negative and not taking ARVs; and the PKs of hormonal contraceptive medications taken along with ARVs.

P1026s is a Phase IV clinical study. Participants were not assigned to the drugs under study, but were already receiving the drugs for clinical care by prescription of 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 drugs were provided as part of this study. This observational study was added to an existing investigational new drug (IND) number because several of the drugs were studied at a higher does than the approved dose after the PK results for the approved dose were found to be inadequate.

P1026s went through 10 protocol versions, with the first and last versions of the protocol finalized in 2002 and 2016, respectively. New study arms were added and analyzed separately with each update of the protocol version. In general, there were five main groups of study arms: HIV-infected pregnant women taking ARVs without TB treatment, HIV-infected pregnant women taking ARVs with first-line TB treatment, HIV-uninfected pregnant women taking no ARVs with first-line TB treatment, HIV-infected and HIV-uninfected pregnant women with or without ARVs with second-line TB treatment for drug-resistant TB, and HIV-infected postpartum women taking ARVs and hormonal contraceptives. The primary analysis of each arm was designed and conducted as a separate single arm evaluation of the drug (or combination of drugs) of interest.

Women who were 20 0/7 weeks to 37 6/7 weeks pregnant were enrolled in this study and remained in the study for up to 12 weeks after delivery. Postpartum women were enrolled at 2 to 12 weeks after delivery and followed until 6 to 7 weeks after starting contraceptives. Infants were enrolled in-utero and followed for 16 to 24 weeks of life. At all study visits, participants underwent a medical history, a physical exam, and blood collection. At some visits, women in some arms underwent a vaginal swab. Blood collection from the mother and the detached umbilical cord occurred during delivery. Intensive PK sampling was performed at study visits during the second and third trimester of pregnancy and/or postpartum, depending on the study arm. Additional study visits may have occurred depending on the ARV drug regimen prescribed. Infant washout PK samples were collected at 2-10, 18-28, 36-72 hours after birth, and 5-9 days of life.

There are a total of 49 study arms across all versions of P1026s protocols. Out of the 49 study arms, 2 did not have PK data\* \[didanosine delayed release (DDI) and lopinavir/ritonavir (LPV/RTV) African sites only\]; 2 never enrolled any participants \[amprenavir (APV) and nevirapine/rifampicin (NVP/RIF) with at least one first line TB drug\]; 9 are in the line to be tested/analyzed due to batched analysis which has to be done after the end of the study, the lengthy process of development, validation and approval (regulatory burdens), and laboratory delays related to the COVID-19 pandemic \[all TB arms and all but 3 contraceptive arms (atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) with etonogestrel (ENG), efavirenz (EFV) with ENG, and LPV/RTV with ENG)\]; and 8 had completion dates earlier than December 26, 2007 \[nevirapine (NVP), abacavir (ABC), LPV/RTV 400/100 mg twice daily (b.i.d.), LPV/RTV 400/100mg then 533/133mg b.i.d, nelfinavir (NFV), emtricitabine (FTC), indinavir/ritonavir (IDV/RTV), and tipranavir/ritonavir\]. In this submission, the Results Section presents participant flow, baseline characteristics and adverse events for all study arms (except the 2 arms that never enrolled), and outcome measure results for the 28 remaining study arms that have been completed and have final results available. For study arms completed prior to December 26, 2007, refer to the study publications in the References section for outcome measures.

For arms with very low enrollment (N\<3), some results throughout the record (e.g. baseline characteristics and outcome measures) were not reported in order to avoid making individual participant data identifiable.

In the Outcome Measures section, there could be multiple outcome measures for same PK parameters (e.g. AUC12) depending on different units or summary statistics used in the analyses (such as median with range vs. median with interquartile range (IQR)).

Study Timeline

• Study First Submitted: 2002-07-26
• Study First Submitted QC: 2002-07-31
• Study First Posted: 2002-08-01
• Study Start: 2003-06-09
• Primary Completion: 2020-09-30
• Study Completion: 2020-09-30
• Results First Submitted: 2021-10-05
• Status Verified: 2022-06
• Results First Submitted QC: 2022-06-28
• Last Update Submitted: 2022-06-28
• Results First Posted: 2022-07-22
• Last Update Posted: 2022-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1578

Inclusion Criteria

• Participant must belong to one of the following 5 groups:

  1. HIV-infected pregnant women greater than or equal to 20 weeks gestation NOT on TB treatment receiving one or more of the ARV drugs/drug combinations specified in the protocol
  2. HIV-infected pregnant women greater than or equal to 20 weeks gestation receiving one of the ARV drugs/drug combinations specified in the protocol and TB treatment with at least one of the TB drugs, specified in the protocol, at study entry
  3. HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the first-line TB drugs, specified in the protocol, at study entry
  4. HIV-infected and HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the second-line TB drugs, specified in the protocol, at study entry
  5. HIV-infected women 2 to 12 weeks (14 to 84 days) post-delivery receiving one of the ARV drug combinations listed in the protocol AND starting postpartum contraceptives as listed in the protocol

• The woman must be stable on the ARV drug/drug combination and/or TB drug combination for at least 2 weeks prior to PK sampling

• If a woman is receiving a specific generic ARV formulation, the protocol team has approved this formulation

• HIV-infected pregnant women must be planning to continue on current ARV regimen until postpartum PK sampling is completed. HIV-infected postpartum women on hormonal contraceptives must be planning to continue on ARV and contraceptive regimens until final PK sampling is completed

• For HIV-infected women: confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry. More information on this criterion can be found in the protocol.

• HIV-uninfected pregnant women must have documented negative HIV antibody test during current pregnancy. Note: adequate source documentation, including the date of specimen collection, date of testing, test performed, and test result, must be available.

• Participants enrolling in the 3rd trimester must enroll by 37 6/7 weeks gestation

• Participant can provide legal informed consent per local regulations

• If a woman has completed this study and becomes pregnant again, she may re-enroll in the study only if she is enrolled in a different arm than that studied during her initial enrollment

Maternal

Exclusion Criteria

• Women on medicines known to interfere with absorption, metabolism, or clearance of the drug being evaluated (see protocol for more information). Rifampicin is permitted for women being evaluated for TB and ARV drug interactions
• If pregnant, carrying multiple fetuses
• Clinical or laboratory toxicity that, in the opinion of the site investigator, would be likely to require a change in the medicine regimen during the period of study

Infant Enrollment Criteria:

• All infants of mothers enrolled during pregnancy (meeting criteria specified above) are enrolled, in utero, immediately after maternal enrollment.

Infant Requirements for Washout Pharmacokinetic Sampling:

• Born to HIV-infected mother enrolled during pregnancy in an ARV arm (does not include infants born to HIV-uninfected mothers receiving TB drugs)
• Birth weight greater than 1000 grams
• Is NOT receiving disallowed medications described in Section 7 of the protocol
• 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
• Born after singleton delivery (not after multiple birth)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
NFV Arm 2: 1250mg b.i.d. then 1875mg b.i.d. then 1250mg b.i.d.	nelfinavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) \[625 mg tablets\] 1250 mg twice a day until 30 weeks gestation; then 1875 mg twice a day until postpartum hospital discharge; then 1250 mg twice a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG	etonogestrel implant	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.	darunavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received: darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn. OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.	darunavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received: darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn. OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
TAF 10mg q.d. w/COBI	TAF w/cobicistat	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received tenofovir alafenamide fumarate (TAF) 10 mg q.d. with cobicistat (COBI).
TAF 25mg q.d. w/COBI or RTV boosting	TAF w/cobicistat or ritonavir	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received tenofovir alafenamide fumarate (TAF) 25 mg q.d. with cobicistat (COBI) or ritonavir (RTV) boosting.
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.	darunavir/ritonavir dosage #3	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received: darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn. OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
TAF 25mg q.d.	tenofovir alafenamide fumarate (TAF)	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received tenofovir alafenamide fumarate (TAF) 25 mg q.d. without cobicistat or ritonavir boosting.
EVG/COBI 150/150mg q.d.	elvitegravir/cobicistat	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received elvitegravir/cobicistat (EVG/COBI) 150/150 mg q.d
DRV/COBI 800/150 mg q.d.	darunavir/cobicistat	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d.
ATV/COBI 300/150 mg q.d.	atazanavir/cobicistat	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d.
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug	lopinavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
At least two 2nd line TB drugs w/ or w/out ARVs	levoflaxacin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	ethionamide/prothionamide	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	terizidone/cycloserine	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	para-aminosalicylic acid (PAS)	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE	atazanavir/cobicistat	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE	darunavir/cobicistat	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG	atazanavir/cobicistat	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG	darunavir/cobicistat	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
ATV/RTV/TFV 300/100/300mg q.d. with 30-35ug EE	atazanavir/ritonavir/tenofovir dosage #1	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
LPV/RTV Arm 1: 400/100mg b.i.d	lopinavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 26 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 400/100mg twice a day
IDV/RTV Arm 1: 800/100mg b.i.d	indinavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 26 weeks gestation who received indinavir/ritonavir (IDV/RTV) 800/100 mg twice a day
FPV/RTV 700/100mg b.i.d.	fosamprenavir/ritonavir	HIV-infected pregnant women ≥ 20 weeks gestation who received fosamprenavir/ritonavir (FPV/RTV)700/100mg twice a day
LPV/RTV Arm 2: 400/100mg b.i.d. then 533/133mg b.i.d.	lopinavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received Kaletra (LPV/RTV) 400/100 mg twice a day until 30 weeks gestation, then 533/133 mg twice a day until results of postpartum PK evaluation were available
LPV/RTV Arm 2: 400/100mg b.i.d. then 533/133mg b.i.d.	lopinavir/ritonavir dosage #3	HIV-infected pregnant women ≥ 20 weeks gestation who received Kaletra (LPV/RTV) 400/100 mg twice a day until 30 weeks gestation, then 533/133 mg twice a day until results of postpartum PK evaluation were available
ATV/RTV Arm 1: 300/100mg q.d.	atazanavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day
DDI 400mg or 250mg q.d.	didanosine delayed release (Videx® EC)	HIV-infected pregnant women ≥ 20 weeks gestation who received didanosine delayed release (Videx® EC) (DDI) 400 mg once a day if weight \> 60 kg; 250 mg once a day if weight \< 60 kg
FTC 200mg q.d.	emtricitabine	HIV-infected pregnant women ≥ 20 weeks gestation who received emtricitabine (FTC) 200 mg once a day
TFV/ATV/RTV Arm 1: 300/300/100mg q.d.	atazanavir/ritonavir/tenofovir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day
NFV Arm 1: 1250mg b.i.d.	nelfinavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) \[625 mg tablets\] 1250 mg twice a day
TPV/RTV 500/200mg b.i.d.	tipranavir/ritonavir	HIV-infected pregnant women ≥ 20 weeks gestation who received tipranavir/ritonavir (TPV/RTV) 500/200 mg twice a day
LPV/RTV Arm 3: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d.	lopinavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) tablets 400/100 mg \[2 tablets\] twice a day until 30 weeks gestation, then 600/150 mg \[3 tablets\] twice a day until postpartum hospital discharge; and 400/100 mg \[2 tablets\] twice a day after postpartum hospital discharge, until 2 week postpartum PK sample is drawn
LPV/RTV Arm 3: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d.	lopinavir/ritonavir dosage #4	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) tablets 400/100 mg \[2 tablets\] twice a day until 30 weeks gestation, then 600/150 mg \[3 tablets\] twice a day until postpartum hospital discharge; and 400/100 mg \[2 tablets\] twice a day after postpartum hospital discharge, until 2 week postpartum PK sample is drawn
ETR 200mg b.i.d.	etravirine	HIV-infected pregnant women ≥ 20 weeks gestation who received etravirine (ETR) 200mg twice a day
TFV/ATV/RTV Arm 2: 300/300/100mg q.d. then 300/400/100mg q.d then 300/300/100mg q.d.	atazanavir/ritonavir/tenofovir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day until 30 weeks gestation; then 300/400/100 mg once a day until postpartum hospital discharge; then 300/300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
TFV/ATV/RTV Arm 2: 300/300/100mg q.d. then 300/400/100mg q.d then 300/300/100mg q.d.	tenofovir/atazanavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day until 30 weeks gestation; then 300/400/100 mg once a day until postpartum hospital discharge; then 300/300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
NFV Arm 2: 1250mg b.i.d. then 1875mg b.i.d. then 1250mg b.i.d.	nelfinavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) \[625 mg tablets\] 1250 mg twice a day until 30 weeks gestation; then 1875 mg twice a day until postpartum hospital discharge; then 1250 mg twice a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
DRV/RTV 800/100mg q.d.	darunavir/ritonavir dosage #4	HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir (DRV/RTV) 800/100 mg once a day
DRV/RTV 600/100mg b.i.d.	darunavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir (DRV/RTV) 600/100 mg twice a day
ATV/RTV Arm 2: 300/100mg q.d. then 400/100mg q.d. then 300/100mg q.d.	atazanavir/ritonavir dosage #1	HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day until 30 weeks gestation then 400/100 mg once a day until postpartum hospital discharge; then 300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
ATV/RTV Arm 2: 300/100mg q.d. then 400/100mg q.d. then 300/100mg q.d.	atazanavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day until 30 weeks gestation then 400/100 mg once a day until postpartum hospital discharge; then 300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
IDV/RTV Arm 2: 400/100mg q.d. (only THA)	indinavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received indinavir/ritonavir (IDV/RTV) 400/100 mg twice a day only to participants enrolling in Thailand
LPV/RTV Arm 4: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d. (only African sites)	lopinavir/ritonavir dosage #2	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV, Alluvia tablets) 400/100 mg \[2 tablets\] twice day until 30 weeks gestation; then 600/150 mg \[3 tablets\] twice a day until postpartum hospital discharge; then 400/100 mg \[2 tablets\] twice a day after postpartum hospital discharge until 2 week postpartum PK sample drawn only to participants enrolling in Uganda
LPV/RTV Arm 4: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d. (only African sites)	lopinavir/ritonavir dosage #4	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV, Alluvia tablets) 400/100 mg \[2 tablets\] twice day until 30 weeks gestation; then 600/150 mg \[3 tablets\] twice a day until postpartum hospital discharge; then 400/100 mg \[2 tablets\] twice a day after postpartum hospital discharge until 2 week postpartum PK sample drawn only to participants enrolling in Uganda
RPV 25mg q.d.	rilpivirine	HIV-infected pregnant women ≥ 20 weeks gestation who received rilpivirine (RPV) (25 mg q.d.)
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug	ethambutol	HIV-infected pregnant women \> 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry: * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
ATV/RTV/TFV 300/100/300mg q.d. with ENG	atazanavir/ritonavir/tenofovir dosage #1	HIV- infected women 2-12 weeks postpartum who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
ATV/RTV/TFV 300/100/300mg q.d. with ENG	etonogestrel implant	HIV- infected women 2-12 weeks postpartum who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
LPV/RTV 400/100 b.i.d. with 30-35ug EE	lopinavir/ritonavir dosage #2	HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
LPV/RTV 400/100 b.i.d. with ENG	etonogestrel implant	HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting postpartum etonogestrel (ENG) implant
LPV/RTV 400/100 b.i.d. with ENG	lopinavir/ritonavir dosage #2	HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting postpartum etonogestrel (ENG) implant
EFV 600mg q.d. with ENG	efavirenz	HIV-infected women 2-12 weeks postpartum who received efavirenz (EFV) 600mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
EFV 600mg q.d. with ENG	etonogestrel implant	HIV-infected women 2-12 weeks postpartum who received efavirenz (EFV) 600mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
At least two 2nd line TB drugs w/ or w/out ARVs	high dose INH	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
RAL 400mg b.i.d.	raltegravir	HIV-infected pregnant women ≥ 20 weeks gestation who received raltegravir (RAL) 400 mg twice a day
EFV 600mg q.d.	efavirenz	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600 mg once a day
DTG 50mg q.d.	dolutegravir	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received dolutegravir (DTG) 50 mg once a day (q.d.).
EFV 600 mg q.d. (outside THA)	efavirenz	HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received efavirenz (EFV) 600 mg q.d. (Participants outside of Thailand only)
EFV 600mg q.d. and at least one 1st line TB drug	efavirenz	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
EFV 600mg q.d. and at least one 1st line TB drug	ethambutol	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
EFV 600mg q.d. and at least one 1st line TB drug	rifampicin	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
EFV 600mg q.d. and at least one 1st line TB drug	isoniazid	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
EFV 600mg q.d. and at least one 1st line TB drug	pyrazinamide	HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug	rifampicin	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug	ethambutol	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug	isoniazid	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug	pyrazinamide	HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
No ARVs and at least two 1st line TB drugs	rifampicin	HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following first line TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
No ARVs and at least two 1st line TB drugs	ethambutol	HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following first line TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
No ARVs and at least two 1st line TB drugs	isoniazid	HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following first line TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
At least two 2nd line TB drugs w/ or w/out ARVs	kanamycin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
No ARVs and at least two 1st line TB drugs	pyrazinamide	HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following first line TB drugs at study entry: * rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
At least two 2nd line TB drugs w/ or w/out ARVs	amikacin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	capreomycin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	moxifloxacin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	ofloxacin	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	bedaquiline	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	clofazamine	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	delamanid	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	linezolid	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
At least two 2nd line TB drugs w/ or w/out ARVs	pretomanid	HIV-infected and HIV-uninfected pregnant women ≥ 20 weeks gestation who received at least two of the following second line TB drugs at study entry: Injectable agents: * kanamycin * amikacin * capreomycin Fluoroquinolones: * moxifloxacin * levofloxacin * ofloxacin Oral bacteriostatic second-line agents: * ethionamide/prothionamide * terizidone/cycloserine * para-aminosalicylic acid (PAS) Other agents: * high dose INH * bedaquiline * clofazamine * delamanid * linezolid * pretomanid
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE	ethinyl estradiol	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
EFV 600mg q.d. with 30-35ug EE	ethinyl estradiol	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received efavirenz (EFV) 600mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
EFV 600mg q.d. with 30-35ug EE	efavirenz	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received efavirenz (EFV) 600mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
NVP 200mg b.i.d	nevirapine	HIV-infected pregnant women ≥ 26 weeks gestation who received nevirapine (NVP) 200 mg twice a day
ATV/RTV/TFV 300/100/300mg q.d. with 30-35ug EE	ethinyl estradiol	HIV-infected women 2-12 weeks (14-84 days) post-delivery who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
APV 1200mg b.i.d	amprenavir	HIV-infected pregnant women ≥ 26 weeks gestation who received amprenavir (APV) 1200mg twice a day
ABC 300mg b.i.d	abacavir	HIV-infected pregnant women ≥ 20 weeks gestation who received abacavir (ABC) 300mg twice a day
TFV 300mg q.d.	tenofovir	HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir (TFV) 300 mg once a day
MVC 150 or 300mg b.i.d.	maraviroc	HIV-infected pregnant women ≥ 20 weeks gestation who received maraviroc (MVC)150 mg or 300 mg twice a day
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug	isoniazid	HIV-infected pregnant women \> 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry: * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug	pyrazinamide	HIV-infected pregnant women \> 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry: * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug	nevirapine	HIV-infected pregnant women \> 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry: * ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w. * isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. * pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
LPV/RTV 400/100 b.i.d. with 30-35ug EE	ethinyl estradiol	HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)

Primary Outcome Measures

Name	Time	Method
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs	Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs	Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs	Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.	Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24 (area under the curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the trapezoidal rule.
PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 12 hrs after an observed dose.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.; For the TAF 25 mg q.d., 10 mg q.d. w/COBI, and 25 mg q.d. w/COBI or RTV boosting arms, samples were all below the limit of quantification and statistical analyses were not conducted.
PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.
Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC (area under the curve) were determined using the linear trapezoidal rule. See PK target in the Protocol Appendix V.
Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs	Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose. See PK target in Protocol Appendix V.; No results are available for this outcome measure at this time. The TB drugs are being assayed in batches (not real-time) after the study completion. Labs have been experiencing additional delays due to urgent COVID-19 pandemic related work.
Plasma Concentration for Contraceptives	Measured at 6-7 weeks after contraceptive initiation postpartum	Serum concentrations of the contraceptives. Note that no historical controls were provided by team pharmacologists and thus no comparisons were done for contraceptive concentrations in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.
Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms	Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8 and 12 hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms	Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8, 12, and 24 hours post dosing.	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the linear trapezoidal rule.

Secondary Outcome Measures

Name	Time	Method
PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs	Measured at time of delivery with single cord blood and single maternal plasma sample.	Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio.
PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs	Measured at time of delivery with single cord blood and single maternal plasma sample.	Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio. For arms with zero overall participants analyzed, samples were below the limit of quantification and ratios could not be calculated.
Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs	Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth.	Infant plasma concentrations were collected and measured during the first 9 days of life. Half-life is defined as 0.693/k, where k, the elimination rate constant, is the slope of the decline in concentrations.
Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs	Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth.	Infant plasma concentrations were collected and measured during the first 9 days of life.

Trial Locations

Locations (62)

Usc La Nichd Crs; 🇺🇸 Los Angeles, California, United States

Wits RHI Shandukani Research Centre CRS; 🇿🇦 Johannesburg, Gauteng, South Africa

Boston Medical Center Ped. HIV Program NICHD CRS; 🇺🇸 Boston, Massachusetts, United States

Seattle Children's Research Institute CRS; 🇺🇸 Seattle, Washington, United States

SOM Federal University Minas Gerais Brazil NICHD CRS; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Univ. of California San Francisco NICHD CRS; 🇺🇸 San Francisco, California, United States

Pediatric Perinatal HIV Clinical Trials Unit CRS; 🇺🇸 Miami, Florida, United States

David Geffen School of Medicine at UCLA NICHD CRS; 🇺🇸 Los Angeles, California, United States

Miller Children's Hosp. Long Beach CA NICHD CRS; 🇺🇸 Long Beach, California, United States

Emory University School of Medicine NICHD CRS; 🇺🇸 Atlanta, Georgia, United States

Columbia IMPAACT CRS; 🇺🇸 New York, New York, United States

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program; 🇺🇸 Chicago, Illinois, United States

Rush Univ. Cook County Hosp. Chicago NICHD CRS; 🇺🇸 Chicago, Illinois, United States

Lurie Children's Hospital of Chicago (LCH) CRS; 🇺🇸 Chicago, Illinois, United States

Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases; 🇺🇸 Augusta, Georgia, United States

Nyu Ny Nichd Crs; 🇺🇸 New York, New York, United States

WNE Maternal Pediatric Adolescent AIDS CRS; 🇺🇸 Worcester, Massachusetts, United States

Metropolitan Hosp. NICHD CRS; 🇺🇸 New York, New York, United States

Regional Med. Ctr. at Memphis; 🇺🇸 Memphis, Tennessee, United States

IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS; 🇵🇷 San Juan, Puerto Rico

Children's Hospital of Michigan NICHD CRS; 🇺🇸 Detroit, Michigan, United States

Chiangrai Prachanukroh Hospital NICHD CRS; 🇹🇭 Chiang Mai, Thailand

Hosp. Geral De Nova Igaucu Brazil NICHD CRS; 🇧🇷 Rio de Janeiro, Brazil

Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS; 🇿🇦 Cape Town, Western Cape Province, South Africa

Gaborone CRS; 🇧🇼 Gaborone, South-East District, Botswana

Univ. of Sao Paulo Brazil NICHD CRS; 🇧🇷 Sao Paulo, Brazil

Hospital Federal dos Servidores do Estado NICHD CRS; 🇧🇷 Rio de Janeiro, Brazil

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS; 🇹🇭 Chiang Mai, Thailand

Bhumibol Adulyadej Hosp. CRS; 🇹🇭 Sai Mai, Bangkok, Thailand

Famcru Crs; 🇿🇦 Tygerberg, Western Cape Province, South Africa

Univ. of Colorado Denver NICHD CRS; 🇺🇸 Aurora, Colorado, United States

USF - Tampa NICHD CRS; 🇺🇸 Tampa, Florida, United States

UAB Pediatric Infectious Diseases CRS; 🇺🇸 Birmingham, Alabama, United States

Kilimanjaro Christian Medical Centre (KCMC); 🇹🇿 Moshi, Tanzania

Washington Hosp. Ctr. NICHD CRS; 🇺🇸 Washington, District of Columbia, United States

Harbor UCLA Medical Ctr. NICHD CRS; 🇺🇸 Torrance, California, United States

Univ. of Florida Jacksonville NICHD CRS; 🇺🇸 Jacksonville, Florida, United States

Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.; 🇺🇸 Chicago, Illinois, United States

Univ. of Maryland Baltimore NICHD CRS; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins Univ. Baltimore NICHD CRS; 🇺🇸 Baltimore, Maryland, United States

Rutgers - New Jersey Medical School CRS; 🇺🇸 Newark, New Jersey, United States

St. Jude Children's Research Hospital CRS; 🇺🇸 Memphis, Tennessee, United States

DUMC Ped. CRS; 🇺🇸 Durham, North Carolina, United States

Philadelphia IMPAACT Unit CRS; 🇺🇸 Philadelphia, Pennsylvania, United States

Molepolole CRS; 🇧🇼 Gaborone, Botswana

Hosp. Santa Casa Porto Alegre Brazil NICHD CRS; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Siriraj Hospital ,Mahidol University NICHD CRS; 🇹🇭 Bangkok, Bangkoknoi, Thailand

Chonburi Hosp. CRS; 🇹🇭 Chon Buri, Thailand

University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program; 🇺🇸 La Jolla, California, United States

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS; 🇧🇷 Rio de Janeiro, Brazil

Hosp. dos Servidores Rio de Janeiro NICHD CRS; 🇧🇷 Rio de Janeiro, Brazil

SUNY Stony Brook NICHD CRS; 🇺🇸 Stony Brook, New York, United States

Children's Hosp. of Boston NICHD CRS; 🇺🇸 Boston, Massachusetts, United States

Baystate Health, Baystate Med. Ctr.; 🇺🇸 Springfield, Massachusetts, United States

San Juan City Hosp. PR NICHD CRS; 🇵🇷 San Juan, Puerto Rico

Hosp. General de Agudos Buenos Aires Argentina NICHD CRS; 🇦🇷 Ciudad de Buenos Aires, Buenos Aires, Argentina

Phayao Provincial Hosp. CRS; 🇹🇭 T.Tom, Muang, Phayao, Thailand

Prapokklao Hosp. CRS; 🇹🇭 Chanthaburi, Thailand

Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease; 🇺🇸 New Haven, Connecticut, United States

Tulane Univ. New Orleans NICHD CRS; 🇺🇸 New Orleans, Louisiana, United States

Bronx-Lebanon Hospital Center NICHD CRS; 🇺🇸 Bronx, New York, United States

Jacobi Med. Ctr. Bronx NICHD CRS; 🇺🇸 Bronx, New York, United States