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

HIV Infections Clinical Trial

Official title:

Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00042289
• Other study ID #: P1026s
• Secondary ID: 10040IMPAACT P10
• Status: Completed
• Start date: June 9, 2003
• Est. completion date: September 30, 2020

Study information

• Verified date: June 2022
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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)).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1578
• Est. completion date: September 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• atazanavir/cobicistat
atazanavir/cobicistat 300/150 mg q.d.
• darunavir/ritonavir dosage #1
darunavir/ritonavir twice daily 600/100 mg b.i.d.
• darunavir/ritonavir dosage #2
darunavir/ritonavir twice daily 800/100 mg b.i.d.
• darunavir/ritonavir dosage #3
darunavir/ritonavir twice daily 900/100 mg b.i.d.
• elvitegravir/cobicistat
elvitegravir/cobicistat 150/150 mg q.d.
• dolutegravir
dolutegravir 50 mg q.d.
• tenofovir alafenamide fumarate (TAF)
TAF 25 mg q.d. without cobicistat or ritonavir boosting
• TAF w/cobicistat
TAF 10 mg q.d. with cobicistat
• TAF w/cobicistat or ritonavir
TAF 25 mg q.d. with cobicistat or ritonavir boosting
• efavirenz
efavirenz 600 mg q.d.
• darunavir/cobicistat
darunavir/cobicistat 800/150 mg q.d.
• lopinavir/ritonavir dosage #1
lopinavir/ritonavir 800/200mg b.i.d.
• atazanavir/ritonavir/tenofovir dosage #1
atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
• rifampicin
rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
• ethambutol
ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
• isoniazid
isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
• pyrazinamide
pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
• kanamycin
kanamycin (2nd line TB drug)
• amikacin
amikacin (2nd line TB drug)
• capreomycin
capreomycin (2nd line TB drug)
• moxifloxacin
moxifloxacin (2nd line TB drug)
• levoflaxacin
levofloxacin (2nd line TB drug)
• ofloxacin
ofloxacin (2nd line TB drug)
• ethionamide/prothionamide
ethionamide/prothionamide (2nd line TB drug)
• terizidone/cycloserine
terizidone/cycloserine (2nd line TB drug)
• para-aminosalicylic acid (PAS)
para-aminosalicylic acid (PAS) (2nd line TB drug)
• high dose INH
high dose INH (2nd line TB drug)
• bedaquiline
bedaquiline (2nd line TB drug)
• clofazamine
clofazamine (2nd TB drug)
• delamanid
delamanid (2nd line TB drug)
• linezolid
linezolid (2nd line TB drug)
• pretomanid
pretomanid (2nd line TB drug)
• ethinyl estradiol
oral contraceptives formulated with 30-35 µg ethinyl estradiol
• etonogestrel implant
etonogestrel implant contraceptive
• nevirapine
nevirapine 200 mg twice a day
• amprenavir
amprenavir 1200mg twice a day
• abacavir
abacavir 300mg twice a day
• lopinavir/ritonavir dosage #2
lopinavir/ritonavir (Kaletra) 400/100mg twice a day
• indinavir/ritonavir dosage #1
indinavir/ritonavir 800/100mg twice a day
• fosamprenavir/ritonavir
fosamprenavir/ritonavir 700/100 mg twice a day
• lopinavir/ritonavir dosage #3
lopinavir/ritonavir (Kaletra) 533/133 mg twice a day
• atazanavir/ritonavir dosage #1
atazanavir/ritonavir 300/100 mg once a day
• 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
• emtricitabine
emtricitabine 200 mg once a day
• tenofovir
tenofovir 300 mg once a day
• nelfinavir dosage #1
nelfinavir [625 mg tablets] 1250 mg twice a day
• tipranavir/ritonavir
tipranavir/ritonavir 500/200 mg twice a day
• lopinavir/ritonavir dosage #4
lopinavir/ritonavir (Kaletra) tablets 600/150 mg [3 tablets] twice a day
• raltegravir
raltegravir 400 mg twice a day
• etravirine
etravirine 200 mg twice a day
• maraviroc
maraviroc 150 mg or 300 mg twice a day
• atazanavir/ritonavir dosage #2
atazanavir/ritonavir 400/100mg once a day
• tenofovir/atazanavir/ritonavir dosage #2
tenofovir/atazanavir/ritonavir 300/400/100 mg once a day
• nelfinavir dosage #2
nelfinavir [625 mg tablets] 1875 mg twice a day
• indinavir/ritonavir dosage #2
indinavir/ritonavir 400/100 mg twice a day
• rilpivirine
rilpivirine (25 mg q.d.)
• darunavir/ritonavir dosage #4
darunavir/ritonavir once daily 800/100 mg q.d.

Locations

Country	Name	City	State
Argentina	Hosp. General de Agudos Buenos Aires Argentina NICHD CRS	Ciudad de Buenos Aires	Buenos Aires
Botswana	Gaborone CRS	Gaborone	South-East District
Botswana	Molepolole CRS	Gaborone
Brazil	SOM Federal University Minas Gerais Brazil NICHD CRS	Belo Horizonte	Minas Gerais
Brazil	Hosp. Santa Casa Porto Alegre Brazil NICHD CRS	Porto Alegre	Rio Grande Do Sul
Brazil	Hosp. dos Servidores Rio de Janeiro NICHD CRS	Rio de Janeiro
Brazil	Hosp. Geral De Nova Igaucu Brazil NICHD CRS	Rio de Janeiro
Brazil	Hospital Federal dos Servidores do Estado NICHD CRS	Rio de Janeiro
Brazil	Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS	Rio de Janeiro
Brazil	Univ. of Sao Paulo Brazil NICHD CRS	Sao Paulo
Puerto Rico	IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS	San Juan
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
South Africa	Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS	Cape Town	Western Cape Province
South Africa	Wits RHI Shandukani Research Centre CRS	Johannesburg	Gauteng
South Africa	Famcru Crs	Tygerberg	Western Cape Province
Tanzania	Kilimanjaro Christian Medical Centre (KCMC)	Moshi
Thailand	Siriraj Hospital ,Mahidol University NICHD CRS	Bangkok	Bangkoknoi
Thailand	Prapokklao Hosp. CRS	Chanthaburi
Thailand	Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital NICHD CRS	Chiang Mai
Thailand	Chonburi Hosp. CRS	Chon Buri
Thailand	Bhumibol Adulyadej Hosp. CRS	Sai Mai	Bangkok
Thailand	Phayao Provincial Hosp. CRS	T.Tom, Muang	Phayao
United States	Emory University School of Medicine NICHD CRS	Atlanta	Georgia
United States	Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Augusta	Georgia
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	Johns Hopkins Univ. Baltimore NICHD CRS	Baltimore	Maryland
United States	Univ. of Maryland Baltimore NICHD CRS	Baltimore	Maryland
United States	UAB Pediatric Infectious Diseases CRS	Birmingham	Alabama
United States	Boston Medical Center Ped. HIV Program NICHD CRS	Boston	Massachusetts
United States	Children's Hosp. of Boston NICHD CRS	Boston	Massachusetts
United States	Bronx-Lebanon Hospital Center NICHD CRS	Bronx	New York
United States	Jacobi Med. Ctr. Bronx NICHD CRS	Bronx	New York
United States	Lurie Children's Hospital of Chicago (LCH) CRS	Chicago	Illinois
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	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	DUMC Ped. CRS	Durham	North Carolina
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program	La Jolla	California
United States	Miller Children's Hosp. Long Beach CA NICHD CRS	Long Beach	California
United States	David Geffen School of Medicine at UCLA NICHD CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	Regional Med. Ctr. at Memphis	Memphis	Tennessee
United States	St. Jude Children's Research Hospital CRS	Memphis	Tennessee
United States	Pediatric Perinatal HIV Clinical Trials Unit CRS	Miami	Florida
United States	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	Columbia IMPAACT CRS	New York	New York
United States	Metropolitan Hosp. NICHD CRS	New York	New York
United States	Nyu Ny Nichd Crs	New York	New York
United States	Rutgers - New Jersey Medical School CRS	Newark	New Jersey
United States	Philadelphia IMPAACT Unit CRS	Philadelphia	Pennsylvania
United States	Univ. of California San Francisco NICHD CRS	San Francisco	California
United States	Seattle Children's Research Institute CRS	Seattle	Washington
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	USF - Tampa NICHD CRS	Tampa	Florida
United States	Harbor UCLA Medical Ctr. NICHD CRS	Torrance	California
United States	Washington Hosp. Ctr. NICHD CRS	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Argentina,  Botswana,  Brazil,  Puerto Rico,  South Africa,  Tanzania,  Thailand, 

References & Publications (37)

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 activi — View Citation

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 pre — View Citation

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 d — View Citation

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. — View Citation

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 pr — View Citation

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 P — View Citation

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 nev — View Citation

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 — View Citation

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 Cli — View Citation

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 Ac — View Citation

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 incre — View Citation

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 Im — View Citation

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 Postpar — View Citation

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). pii: e021 — View Citation

Eke AC, Wang J, Amin K, Shapiro DE, Stek A, Smith E, Chakhtoura N, Basar M, George K, Knapp KM, João EC, Rungruengthanakit K, Capparelli E, Burchett S, Mirochnick M, Best BM; P1026s Protocol Team. Fosamprenavir with Ritonavir Pharmacokinetics during Pregn — View Citation

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 trimeste — View Citation

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. — View Citation

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 — View Citation

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 Modelin — View Citation

Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88. Review. — View Citation

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. — View Citation

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;5 — View Citation

Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-87. Review. — View Citation

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 postpa — View Citation

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 c — View Citation

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 Ma — View Citation

Mulligan N, Schalkwijk S, Best BM, Colbers A, Wang J, Capparelli EV, Moltó 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. Fro — View Citation

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. Review. — View Citation

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 — View Citation

Schalkwijk S, Ter Heine R, Colbers A, Capparelli E, Best BM, Cressey TR, Greupink R, Russel FGM, Moltó J, Mirochnick M, Karlsson MO, Burger DM. Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacok — View Citation

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 R — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. Review. — View Citation

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 — View Citation

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 — View Citation

* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ARV Concentrations in Plasma	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).	Measured at intensive PK visit
Other	ARV Concentrations in Vaginal Secretions	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).	Measured at intensive PK visit
Other	Drug Parameter: Half-life (t1/2)	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).	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.
Other	Drug Parameter: Volume of Distribution Over Systemic Availability (V/F)	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).	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.
Other	Drug Parameter: Clearance Over Systemic Availability (Cl/F)	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).	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.
Other	Drug Parameter: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax)	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).	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.
Other	Drug Parameter: Minimum Concentration (Cmin)	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).	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.
Other	Drug Parameter: Pre-dose Concentration (Cdose)	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).	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.
Other	Adverse Events of Grade 3 or Higher	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.	Measured through 24 weeks postpartum
Other	Infant Neurological Events of Grade 1 or Higher	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.	Measured through 24 weeks of life
Other	Adverse Pregnancy Outcome: Preterm Birth	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.	Measured through delivery
Other	Adverse Pregnancy Outcome: Low Birth Weight	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.	Measured at delivery
Other	Adverse Pregnancy Outcome: Fetal Demise	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.	Measured through 24 weeks postpartum
Other	Adverse Pregnancy Outcome: Congenital Anomalies	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.	Measured through 24 weeks of life
Other	Infant HIV Infection Status	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).	Measured through 24 weeks of life
Other	Ratio of Unbound/Total Drug Concentrations	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).	Measured at time of delivery
Other	Rate of Detection of Study Drugs in Vaginal Secretions	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).	Measured at intensive PK visit
Other	Ratio of Vaginal Drug Concentrations to Simultaneous Blood Concentrations	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).	Measured at intensive PK visit
Other	Rate of Detection of HIV RNA/DNA in Vaginal Secretions and Comparison to Level in Blood	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).	Measured at intensive PK visit
Other	ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype	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).	Measured at intensive PK visit
Primary	PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs	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.	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.
Primary	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.
Primary	PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.	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.
Primary	PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.	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.
Primary	PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.	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.
Primary	PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs	Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.	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.
Primary	PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs	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.	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.
Primary	PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs	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.	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.
Primary	Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs	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.	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.
Primary	Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs	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.	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.
Primary	Plasma Concentration for Contraceptives	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.	Measured at 6-7 weeks after contraceptive initiation postpartum
Primary	Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms	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.	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.
Primary	Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms	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.	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.
Secondary	PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs	Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio.	Measured at time of delivery with single cord blood and single maternal plasma sample.
Secondary	PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs	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.	Measured at time of delivery with single cord blood and single maternal plasma sample.
Secondary	Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs	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.	Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth.
Secondary	Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs	Infant plasma concentrations were collected and measured during the first 9 days of life.	Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth.

External Links

•   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