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

• ClinicalTrials.gov Identifier: NCT00042289
• Recruitment Status: Completed
• First Posted: August 1, 2002
• Results First Posted: July 22, 2022
• Last Update Posted: July 22, 2022
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease

Intervention/treatment

HIV Infections

Drug: atazanavir/cobicistat; Drug: darunavir/ritonavir dosage #1; Drug: darunavir/ritonavir dosage #2; Drug: darunavir/ritonavir dosage #3; Drug: elvitegravir/cobicistat; Drug: dolutegravir; Drug: tenofovir alafenamide fumarate (TAF); Drug: TAF w/cobicistat; Drug: TAF w/cobicistat or ritonavir; Drug: efavirenz; Drug: darunavir/cobicistat; Drug: lopinavir/ritonavir dosage #1; Drug: atazanavir/ritonavir/tenofovir dosage #1; Drug: rifampicin; Drug: ethambutol; Drug: isoniazid; Drug: pyrazinamide; Drug: kanamycin; Drug: amikacin; Drug: capreomycin; Drug: moxifloxacin; Drug: levoflaxacin; 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; Drug: ethinyl estradiol; Drug: etonogestrel implant; Drug: nevirapine; Drug: amprenavir; Drug: abacavir; Drug: lopinavir/ritonavir dosage #2; Drug: indinavir/ritonavir dosage #1; Drug: fosamprenavir/ritonavir; Drug: lopinavir/ritonavir dosage #3; Drug: atazanavir/ritonavir dosage #1; Drug: didanosine delayed release (Videx® EC); Drug: emtricitabine; Drug: tenofovir; Drug: nelfinavir dosage #1; Drug: tipranavir/ritonavir; Drug: lopinavir/ritonavir dosage #4; Drug: raltegravir; Drug: etravirine; Drug: maraviroc; Drug: atazanavir/ritonavir dosage #2; Drug: tenofovir/atazanavir/ritonavir dosage #2; Drug: nelfinavir dosage #2; Drug: indinavir/ritonavir dosage #2; Drug: rilpivirine; Drug: darunavir/ritonavir dosage #4

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 Design

• Study Type: Observational
• Actual Enrollment: 1578 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
• Actual Study Start Date: June 9, 2003
• Actual Primary Completion Date: September 30, 2020
• Actual Study Completion Date: September 30, 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
2. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
3. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs [ Time Frame: 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.
4. PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
5. PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
6. PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
7. PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
8. PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
9. PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs [ Time Frame: 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.
10. PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
11. PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
12. PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs [ Time Frame: 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.
13. PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.

14. PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
15. Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs [ Time Frame: 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.
16. Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs [ Time Frame: 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.

17. Plasma Concentration for Contraceptives [ Time Frame: 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.
18. Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms [ Time Frame: 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.
19. Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms [ Time Frame: 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 :

1. PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs [ Time Frame: 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.
2. PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs [ Time Frame: 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.
3. Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs [ Time Frame: 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.
4. Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs [ Time Frame: 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.

Other Outcome Measures:

1. ARV Concentrations in Plasma [ Time Frame: Measured at intensive PK visit ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belong with Other outcome measures (see SAP).
2. ARV Concentrations in Vaginal Secretions [ Time Frame: Measured at intensive PK visit ]
   The original study protocol listed this PK parameter under secondary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
3. Drug Parameter: Half-life (t1/2) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 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. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
4. Drug Parameter: Volume of Distribution Over Systemic Availability (V/F) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
5. Drug Parameter: Clearance Over Systemic Availability (Cl/F) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 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. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
6. Drug Parameter: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 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. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
7. Drug Parameter: Minimum Concentration (Cmin) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
8. Drug Parameter: Pre-dose Concentration (Cdose) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 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. ]
   The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
9. Adverse Events of Grade 3 or Higher [ Time Frame: Measured through 24 weeks postpartum ]

   The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

   See Adverse events section for adverse events.

10. Infant Neurological Events of Grade 1 or Higher [ Time Frame: Measured through 24 weeks of life ]

    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

    See Adverse events section for adverse events.

11. Adverse Pregnancy Outcome: Preterm Birth [ Time Frame: Measured through delivery ]

    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

    See Adverse events section for adverse events.

12. Adverse Pregnancy Outcome: Low Birth Weight [ Time Frame: Measured at delivery ]

    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

    See Adverse events section for adverse events.

13. Adverse Pregnancy Outcome: Fetal Demise [ Time Frame: Measured through 24 weeks postpartum ]

    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

    See Adverse events section for adverse events.

14. Adverse Pregnancy Outcome: Congenital Anomalies [ Time Frame: Measured through 24 weeks of life ]

    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which werenot conducted (see SAP).

    See Adverse events section for adverse events.

15. Infant HIV Infection Status [ Time Frame: Measured through 24 weeks of life ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
16. Ratio of Unbound/Total Drug Concentrations [ Time Frame: Measured at time of delivery ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
17. Rate of Detection of Study Drugs in Vaginal Secretions [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
18. Ratio of Vaginal Drug Concentrations to Simultaneous Blood Concentrations [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
19. Rate of Detection of HIV RNA/DNA in Vaginal Secretions and Comparison to Level in Blood [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
20. ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Pregnant and postpartum women from IMPAACT US and non-US sites receiving the medicines specified in the protocol as part of clinical care and infants born to those women enrolled during pregnancy.

Criteria

Maternal 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)

Contacts and Locations

Locations

United States, Alabama

UAB Pediatric Infectious Diseases CRS

Birmingham, Alabama, United States, 35233

United States, California

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

La Jolla, California, United States, 92093-0672

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States, 90806

Usc La Nichd Crs

Los Angeles, California, United States, 90089

David Geffen School of Medicine at UCLA NICHD CRS

Los Angeles, California, United States, 90095-1752

Univ. of California San Francisco NICHD CRS

San Francisco, California, United States, 94143

Harbor UCLA Medical Ctr. NICHD CRS

Torrance, California, United States, 90502

United States, Colorado

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Washington Hosp. Ctr. NICHD CRS

Washington, District of Columbia, United States, 20010

United States, Florida

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, United States, 32209

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, United States, 33136

USF - Tampa NICHD CRS

Tampa, Florida, United States, 33606

United States, Georgia

Emory University School of Medicine NICHD CRS

Atlanta, Georgia, United States, 30322

Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases

Augusta, Georgia, United States, 30912

United States, Illinois

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program

Chicago, Illinois, United States, 60608

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, United States, 60612

Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.

Chicago, Illinois, United States, 60612

Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, United States, 60614-3393

United States, Louisiana

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, United States, 70112

United States, Maryland

Univ. of Maryland Baltimore NICHD CRS

Baltimore, Maryland, United States, 21201

Johns Hopkins Univ. Baltimore NICHD CRS

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, United States, 02115

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, United States, 02118

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States, 01199

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States, 01605

United States, Michigan

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, United States, 48201

United States, New Jersey

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States, 07103

United States, New York

Bronx-Lebanon Hospital Center NICHD CRS

Bronx, New York, United States, 10457

Jacobi Med. Ctr. Bronx NICHD CRS

Bronx, New York, United States, 10461

Nyu Ny Nichd Crs

New York, New York, United States, 10016

Metropolitan Hosp. NICHD CRS

New York, New York, United States, 10029

Columbia IMPAACT CRS

New York, New York, United States, 10032

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States, 11794

United States, North Carolina

DUMC Ped. CRS

Durham, North Carolina, United States, 27710

United States, Pennsylvania

Philadelphia IMPAACT Unit CRS

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Regional Med. Ctr. at Memphis

Memphis, Tennessee, United States, 38103

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, United States, 38105-3678

United States, Washington

Seattle Children's Research Institute CRS

Seattle, Washington, United States, 98101

Argentina

Hosp. General de Agudos Buenos Aires Argentina NICHD CRS

Ciudad de Buenos Aires, Buenos Aires, Argentina, C1221ADC

Botswana

Gaborone CRS

Gaborone, South-East District, Botswana

Molepolole CRS

Gaborone, Botswana

Brazil

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, Brazil, 30.130-100

Hosp. Santa Casa Porto Alegre Brazil NICHD CRS

Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090

Hosp. dos Servidores Rio de Janeiro NICHD CRS

Rio de Janeiro, Brazil, 20221-903

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, Brazil, 20221-903

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS

Rio de Janeiro, Brazil, 21941-612

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, Brazil, 26030

Univ. of Sao Paulo Brazil NICHD CRS

Sao Paulo, Brazil, 14049-900

Puerto Rico

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

San Juan, Puerto Rico, 00935

San Juan City Hosp. PR NICHD CRS

San Juan, Puerto Rico, 00936

South Africa

Wits RHI Shandukani Research Centre CRS

Johannesburg, Gauteng, South Africa, 2001

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

Cape Town, Western Cape Province, South Africa, 7505

Famcru Crs

Tygerberg, Western Cape Province, South Africa, 7505

Tanzania

Kilimanjaro Christian Medical Centre (KCMC)

Moshi, Tanzania

Thailand

Siriraj Hospital ,Mahidol University NICHD CRS

Bangkok, Bangkoknoi, Thailand, 10700

Bhumibol Adulyadej Hosp. CRS

Sai Mai, Bangkok, Thailand, 10220

Phayao Provincial Hosp. CRS

T.Tom, Muang, Phayao, Thailand, 56000

Prapokklao Hosp. CRS

Chanthaburi, Thailand, 22000

Chiangrai Prachanukroh Hospital NICHD CRS

Chiang Mai, Thailand, 50100

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, Thailand, 50200

Chonburi Hosp. CRS

Chon Buri, Thailand, 20000

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Chair: Mark Mirochnick, MD; Boston Medical Center

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol: P1026s Protocol Version 10.0_02Feb2016  [PDF] February 2, 2016

Study Protocol: P1026s Protocol Version 10.0_Letter of Amendment 1_14Dec2016  [PDF] December 14, 2016

Study Protocol: P1026s Protocol Version 10.0_Letter of Amendment 2_13Apr2018  [PDF] April 13, 2018

Statistical Analysis Plan: PK SAP  [PDF] July 27, 2021

Statistical Analysis Plan: Primary SAP  [PDF] September 13, 2021

Informed Consent Form  [PDF] February 2, 2016

More Information

Additional Information:

Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017) 

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010 

Publications of Results:

Best BM, Mirochnick M, Capparelli EV, Stek A, Burchett SK, Holland DT, Read JS, Smith E, Hu C, Spector SA, Connor JD; PACTG P1026s Study Team. Impact of pregnancy on abacavir pharmacokinetics. AIDS. 2006 Feb 28;20(4):553-60. doi: 10.1097/01.aids.0000210609.52836.d1.

Stek AM, Mirochnick M, Capparelli E, Best BM, Hu C, Burchett SK, Elgie C, Holland DT, Smith E, Tuomala R, Cotter A, Read JS. Reduced lopinavir exposure during pregnancy. AIDS. 2006 Oct 3;20(15):1931-9. doi: 10.1097/01.aids.0000247114.43714.90.

Aweeka FT, Stek A, Best BM, Hu C, Holland D, Hermes A, Burchett SK, Read J, Mirochnick M, Capparelli EV; International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team. Lopinavir protein binding in HIV-1-infected pregnant women. HIV Med. 2010 Apr;11(4):232-8. doi: 10.1111/j.1468-1293.2009.00767.x. Epub 2009 Dec 3.

Mirochnick M, Best BM, Stek AM, Capparelli EV, Hu C, Burchett SK, Rossi SS, Hawkins E, Basar M, Smith E, Read JS; IMPAACT 1026s Study Team. Atazanavir pharmacokinetics with and without tenofovir during pregnancy. J Acquir Immune Defic Syndr. 2011 Apr 15;56(5):412-9. doi: 10.1097/QAI.0b013e31820fd093.

Capparelli EV, Aweeka F, Hitti J, Stek A, Hu C, Burchett SK, Best B, Smith E, Read JS, Watts H, Nachman S, Thorpe EM Jr, Spector SA, Jimenez E, Shearer WT, Foca M, Mirochnick M; PACTG 1026S Study Team; PACTG P1022 Study Team. Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics. HIV Med. 2008 Apr;9(4):214-20. doi: 10.1111/j.1468-1293.2008.00553.x.

Mirochnick M, Best BM, Stek AM, Capparelli E, Hu C, Burchett SK, Holland DT, Smith E, Gaddipati S, Read JS; PACTG 1026s Study Team. Lopinavir exposure with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):485-91. doi: 10.1097/QAI.0b013e318186edd0.

Read JS, Best BM, Stek AM, Hu C, Capparelli EV, Holland DT, Burchett SK, Smith ME, Sheeran EC, Shearer WT, Febo I, Mirochnick M. Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum. HIV Med. 2008 Nov;9(10):875-82. doi: 10.1111/j.1468-1293.2008.00640.x. Epub 2008 Sep 14.

Best BM, Stek AM, Mirochnick M, Hu C, Li H, Burchett SK, Rossi SS, Smith E, Read JS, Capparelli EV; International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s Study Team. Lopinavir tablet pharmacokinetics with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2010 Aug;54(4):381-8. doi: 10.1097/qai.0b013e3181d6c9ed.

Stek AM, Best BM, Luo W, Capparelli E, Burchett S, Hu C, Li H, Read JS, Jennings A, Barr E, Smith E, Rossi SS, Mirochnick M. Effect of pregnancy on emtricitabine pharmacokinetics. HIV Med. 2012 Apr;13(4):226-35. doi: 10.1111/j.1468-1293.2011.00965.x. Epub 2011 Nov 30.

Cressey TR, Stek A, Capparelli E, Bowonwatanuwong C, Prommas S, Sirivatanapa P, Yuthavisuthi P, Neungton C, Huo Y, Smith E, Best BM, Mirochnick M; IMPAACT P1026s Team. Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):245-52. doi: 10.1097/QAI.0b013e31823ff052.

Cressey TR, Best BM, Achalapong J, Stek A, Wang J, Chotivanich N, Yuthavisuthi P, Suriyachai P, Prommas S, Shapiro DE, Watts DH, Smith E, Capparelli E, Kreitchmann R, Mirochnick M; IMPAACT P1026s team. Reduced indinavir exposure during pregnancy. Br J Clin Pharmacol. 2013 Sep;76(3):475-83. doi: 10.1111/bcp.12078.

Kreitchmann R, Best BM, Wang J, Stek A, Caparelli E, Watts DH, Smith E, Shapiro DE, Rossi S, Burchett SK, Hawkins E, Byroads M, Cressey TR, Mirochnick M. Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy. J Acquir Immune Defic Syndr. 2013 May 1;63(1):59-66. doi: 10.1097/QAI.0b013e318289b4d2.

Watts DH, Stek A, Best BM, Wang J, Capparelli EV, Cressey TR, Aweeka F, Lizak P, Kreitchmann R, Burchett SK, Shapiro DE, Hawkins E, Smith E, Mirochnick M; IMPAACT 1026s study team. Raltegravir pharmacokinetics during pregnancy. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):375-81. doi: 10.1097/QAI.0000000000000318.

Cressey TR, Urien S, Capparelli EV, Best BM, Buranabanjasatean S, Limtrakul A, Rawangban B, Sabsanong P, Treluyer JM, Jourdain G, Stek A, Lallemant M, Mirochnick M. Impact of body weight and missed doses on lopinavir concentrations with standard and increased lopinavir/ritonavir doses during late pregnancy. J Antimicrob Chemother. 2015 Jan;70(1):217-24. doi: 10.1093/jac/dku367. Epub 2014 Sep 25.

Aweeka FT, Hu C, Huang L, Best BM, Stek A, Lizak P, Burchett SK, Read JS, Watts H, Mirochnick M, Capparelli EV; International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team. Alteration in cytochrome P450 3A4 activity as measured by a urine cortisol assay in HIV-1-infected pregnant women and relationship to antiretroviral pharmacokinetics. HIV Med. 2015 Mar;16(3):176-83. doi: 10.1111/hiv.12195. Epub 2014 Nov 18.

Colbers A, Best B, Schalkwijk S, Wang J, Stek A, Hidalgo Tenorio C, Hawkins D, Taylor G, Kreitchmann R, Burchett S, Haberl A, Kabeya K, van Kasteren M, Smith E, Capparelli E, Burger D, Mirochnick M; PANNA Network and the IMPAACT 1026 Study Team. Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women. Clin Infect Dis. 2015 Nov 15;61(10):1582-9. doi: 10.1093/cid/civ587. Epub 2015 Jul 22.

Best BM, Burchett S, Li H, Stek A, Hu C, Wang J, Hawkins E, Byroads M, Watts DH, Smith E, Fletcher CV, Capparelli EV, Mirochnick M; International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team. Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Med. 2015 Sep;16(8):502-11. doi: 10.1111/hiv.12252. Epub 2015 May 11.

Stek A, Best BM, Wang J, Capparelli EV, Burchett SK, Kreitchmann R, Rungruengthanakit K, Cressey TR, Mofenson LM, Smith E, Shapiro D, Mirochnick M. Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women. J Acquir Immune Defic Syndr. 2015 Sep 1;70(1):33-41. doi: 10.1097/QAI.0000000000000668.

Tran AH, Best BM, Stek A, Wang J, Capparelli EV, Burchett SK, Kreitchmann R, Rungruengthanakit K, George K, Cressey TR, Chakhtoura N, Smith E, Shapiro DE, Mirochnick M; IMPAACT P1026s Protocol Team. Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women. J Acquir Immune Defic Syndr. 2016 Jul 1;72(3):289-96. doi: 10.1097/QAI.0000000000000968.

Mulligan N, Schalkwijk S, Best BM, Colbers A, Wang J, Capparelli EV, Molto J, Stek AM, Taylor G, Smith E, Hidalgo Tenorio C, Chakhtoura N, van Kasteren M, Fletcher CV, Mirochnick M, Burger D. Etravirine Pharmacokinetics in HIV-Infected Pregnant Women. Front Pharmacol. 2016 Aug 4;7:239. doi: 10.3389/fphar.2016.00239. eCollection 2016.

Mulligan N, Best BM, Wang J, Capparelli EV, Stek A, Barr E, Buschur SL, Acosta EP, Smith E, Chakhtoura N, Burchett S, Mirochnick M; IMPAACT P1026s Protocol Team. Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV. AIDS. 2018 Mar 27;32(6):729-737. doi: 10.1097/QAD.0000000000001755.

Schalkwijk S, Ter Heine R, Colbers AC, Huitema ADR, Denti P, Dooley KE, Capparelli E, Best BM, Cressey TR, Greupink R, Russel FGM, Mirochnick M, Burger DM. A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women. Clin Pharmacokinet. 2018 Nov;57(11):1421-1433. doi: 10.1007/s40262-018-0642-9.

Eke AC, Chakhtoura N, Kashuba A, Best BM, Sykes C, Wang J, Stek AM, Smith E, Calabrese S, Capparelli EV, Mirochnick M; IMPAACT P1026s Protocol Team. Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum. J Acquir Immune Defic Syndr. 2018 Jul 1;78(3):308-313. doi: 10.1097/QAI.0000000000001677.

Momper JD, Best BM, Wang J, Capparelli EV, Stek A, Barr E, Badell ML, Acosta EP, Purswani M, Smith E, Chakhtoura N, Park K, Burchett S, Shapiro DE, Mirochnick M; IMPAACT P1026s Protocol Team. Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. AIDS. 2018 Nov 13;32(17):2507-2516. doi: 10.1097/QAD.0000000000001992.

Eke AC, McCormack SA, Best BM, Stek AM, Wang J, Kreitchmann R, Shapiro D, Smith E, Mofenson LM, Capparelli EV, Mirochnick M; IMPAACT P1026s Protocol Team. Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum. J Clin Pharmacol. 2019 Mar;59(3):386-393. doi: 10.1002/jcph.1331. Epub 2018 Oct 25.

Kreitchmann R, Schalkwijk S, Best B, Wang J, Colbers A, Stek A, Shapiro D, Cressey T, Mirochnick M, Burger D. Efavirenz pharmacokinetics during pregnancy and infant washout. Antivir Ther. 2019;24(2):95-103. doi: 10.3851/IMP3283.

Schalkwijk S, Ter Heine R, Colbers A, Capparelli E, Best BM, Cressey TR, Greupink R, Russel FGM, Molto J, Mirochnick M, Karlsson MO, Burger DM. Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling. J Antimicrob Chemother. 2019 May 1;74(5):1348-1356. doi: 10.1093/jac/dky567.

Liu XI, Momper JD, Rakhmanina N, van den Anker JN, Green DJ, Burckart GJ, Best BM, Mirochnick M, Capparelli EV, Dallmann A. Physiologically Based Pharmacokinetic Models to Predict Maternal Pharmacokinetics and Fetal Exposure to Emtricitabine and Acyclovir. J Clin Pharmacol. 2020 Feb;60(2):240-255. doi: 10.1002/jcph.1515. Epub 2019 Sep 6.

Eke AC, Wang J, Amin K, Shapiro DE, Stek A, Smith E, Chakhtoura N, Basar M, George K, Knapp KM, Joao EC, Rungruengthanakit K, Capparelli E, Burchett S, Mirochnick M, Best BM; P1026s Protocol Team. Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e02260-19. doi: 10.1128/AAC.02260-19. Print 2020 Mar 24.

Liu XI, Momper JD, Rakhmanina NY, Green DJ, Burckart GJ, Cressey TR, Mirochnick M, Best BM, van den Anker JN, Dallmann A. Prediction of Maternal and Fetal Pharmacokinetics of Dolutegravir and Raltegravir Using Physiologically Based Pharmacokinetic Modeling. Clin Pharmacokinet. 2020 Nov;59(11):1433-1450. doi: 10.1007/s40262-020-00897-9.

Brooks KM, Momper JD, Pinilla M, Stek AM, Barr E, Weinberg A, Deville JG, Febo IL, Cielo M, George K, Denson K, Rungruengthanakit K, Shapiro DE, Smith E, Chakhtoura N, Rooney JF, Haubrich R, Espina R, Capparelli EV, Mirochnick M, Best BM; IMPAACT P1026s Protocol Team. Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV. AIDS. 2021 Mar 1;35(3):407-417. doi: 10.1097/QAD.0000000000002767.

Eke AC, Shoji K, Best BM, Momper JD, Stek AM, Cressey TR, Mirochnick M, Capparelli EV. Population Pharmacokinetics of Tenofovir in Pregnant and Postpartum Women Using Tenofovir Disoproxil Fumarate. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02168-20. doi: 10.1128/AAC.02168-20. Print 2021 Feb 17.

Momper JD, Wang J, Stek A, Shapiro DE, Scott GB, Paul ME, Febo IL, Burchett S, Smith E, Chakhtoura N, Denson K, Rungruengthanakit K, George K, Yang DZ, Capparelli EV, Mirochnick M, Best BM; IMPAACT P1026s Protocol Team. Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV. AIDS. 2021 Jul 1;35(8):1191-1199. doi: 10.1097/QAD.0000000000002857.

Other Publications:

Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88. doi: 10.2165/00003495-200464050-00002.

Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-87. doi: 10.2165/00003088-200443150-00002.

Rakhmanina NY, van den Anker JN, Soldin SJ. Safety and pharmacokinetics of antiretroviral therapy during pregnancy. Ther Drug Monit. 2004 Apr;26(2):110-5. doi: 10.1097/00007691-200404000-00004.

Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. doi: 10.1097/00126334-200309011-00010.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Momper JD, Wang J, Stek A, Shapiro DE, Powis KM, Paul ME, Badell ML, Browning R, Chakhtoura N, Denson K, Rungruengthanakit K, George K, Capparelli EV, Mirochnick M, Best BM; IMPAACT P1026s Protocol Team. Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV. J Acquir Immune Defic Syndr. 2022 Mar 1;89(3):303-309. doi: 10.1097/QAI.0000000000002856.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00042289
• Other Study ID Numbers: P1026s; 10040 ( Registry Identifier: DAIDS ES ); IMPAACT P1026s
• First Posted: August 1, 2002
• Results First Posted: July 22, 2022
• Last Update Posted: July 22, 2022
• Last Verified: June 2022

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Pregnancy; Pharmacokinetics; Treatment Experienced

Additional relevant MeSH terms:

HIV Infections; 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; Ritonavir; Lopinavir; Atazanavir Sulfate; Darunavir; Nelfinavir; Indinavir; Fosamprenavir; Amprenavir; Tenofovir; Emtricitabine; Raltegravir Potassium; Nevirapine; Dolutegravir; Maraviroc; Abacavir; Didanosine