HIV InfectionsNCT00042289
Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 62 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- atazanavir/cobicistat, darunavir/ritonavir dosage #1 and darunavir/ritonavir dosage #2
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 1,578 participants
- Where
- 62 sitesin 8 countries
- Study dates
- 9 Jun 2003to 30 Sep 2020
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Maternal Inclusion Criteria:
- Participant must belong to one of the following 5 groups:
- 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
- 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
- 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
- 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
- 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)
Trial locations and contacts
62 sites in 8 countries.
62 sites in 8 countries
United States39 sites
Emory University School of Medicine NICHD CRS
Atlanta, Georgia, 30322
Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases
Augusta, Georgia, 30912
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Univ. of Maryland Baltimore NICHD CRS
Baltimore, Maryland, 21201
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, 21287
UAB Pediatric Infectious Diseases CRS
Birmingham, Alabama, 35233
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, 02115
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, 02118
Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
Chicago, Illinois, 60608
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, 60612
Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.
Chicago, Illinois, 60612
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
Children's Hospital of Michigan NICHD CRS
Detroit, Michigan, 48201
DUMC Ped. CRS
Durham, North Carolina, 27710
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, 32209
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
La Jolla, California, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, 90806
Usc La Nichd Crs
Los Angeles, California, 90089
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
Regional Med. Ctr. at Memphis
Memphis, Tennessee, 38103
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, 33136
Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
New Haven, Connecticut, 06510
Tulane Univ. New Orleans NICHD CRS
New Orleans, Louisiana, 70112
Nyu Ny Nichd Crs
New York, New York, 10016
Metropolitan Hosp. NICHD CRS
New York, New York, 10029
Columbia IMPAACT CRS
New York, New York, 10032
Rutgers - New Jersey Medical School CRS
Newark, New Jersey, 07103
Philadelphia IMPAACT Unit CRS
Philadelphia, Pennsylvania, 19104
Univ. of California San Francisco NICHD CRS
San Francisco, California, 94143
Seattle Children's Research Institute CRS
Seattle, Washington, 98101
Baystate Health, Baystate Med. Ctr.
Springfield, Massachusetts, 01199
SUNY Stony Brook NICHD CRS
Stony Brook, New York, 11794
USF - Tampa NICHD CRS
Tampa, Florida, 33606
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, 10457
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, 10461
Harbor UCLA Medical Ctr. NICHD CRS
Torrance, California, 90502
Washington Hosp. Ctr. NICHD CRS
Washington D.C., District of Columbia, 20010
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, 01605
Brazil7 sites
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30.130-100
Hosp. Santa Casa Porto Alegre Brazil NICHD CRS
Porto Alegre, Rio Grande do Sul, 90020-090
Hosp. dos Servidores Rio de Janeiro NICHD CRS
Rio de Janeiro, 20221-903
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
Rio de Janeiro, 21941-612
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, 26030
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900
Thailand7 sites
Siriraj Hospital ,Mahidol University NICHD CRS
Bangkok, Bangkoknoi, 10700
Prapokklao Hosp. CRS
Chanthaburi, 22000
Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Mai, 50100
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
Chonburi Hosp. CRS
Chon Buri, 20000
Bhumibol Adulyadej Hosp. CRS
Sai Mai, Bangkok, 10220
Phayao Provincial Hosp. CRS
T.Tom, Muang, Changwat Phayao, 56000
South Africa3 sites
Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
Cape Town, Western Cape, 7505
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001
Famcru Crs
Tygerberg, Western Cape, 7505
Botswana2 sites
Gaborone CRS
Gaborone, South-East District
Molepolole CRS
Gaborone
Puerto Rico2 sites
IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS
San Juan, 00935
San Juan City Hosp. PR NICHD CRS
San Juan, 00936
Argentina1 site
Hosp. General de Agudos Buenos Aires Argentina NICHD CRS
Ciudad de Buenos Aires, Buenos Aires, C1221ADC
About this study
Official title: Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
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.
Read the 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)).
- Conditions
- HIV Infections
- Being tested
- atazanavir/cobicistat, darunavir/ritonavir dosage #1, darunavir/ritonavir dosage #2, darunavir/ritonavir dosage #3, elvitegravir/cobicistat
- Keywords
- Pregnancy, Pharmacokinetics, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atazanavir/cobicistatDrug
atazanavir/cobicistat 300/150 mg q.d.
darunavir/ritonavir dosage #1Drug
darunavir/ritonavir twice daily 600/100 mg b.i.d.
darunavir/ritonavir dosage #2Drug
darunavir/ritonavir twice daily 800/100 mg b.i.d.
darunavir/ritonavir dosage #3Drug
darunavir/ritonavir twice daily 900/100 mg b.i.d.
elvitegravir/cobicistatDrug
elvitegravir/cobicistat 150/150 mg q.d.
dolutegravirDrug
dolutegravir 50 mg q.d.
tenofovir alafenamide fumarate (TAF)Drug
TAF 25 mg q.d. without cobicistat or ritonavir boosting
TAF w/cobicistatDrug
TAF 10 mg q.d. with cobicistat
TAF w/cobicistat or ritonavirDrug
TAF 25 mg q.d. with cobicistat or ritonavir boosting
efavirenzDrug
efavirenz 600 mg q.d.
darunavir/cobicistatDrug
darunavir/cobicistat 800/150 mg q.d.
lopinavir/ritonavir dosage #1Drug
lopinavir/ritonavir 800/200mg b.i.d.
atazanavir/ritonavir/tenofovir dosage #1Drug
atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
rifampicinDrug
rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
ethambutolDrug
ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
isoniazidDrug
isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
pyrazinamideDrug
pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
kanamycinDrug
kanamycin (2nd line TB drug)
amikacinDrug
amikacin (2nd line TB drug)
capreomycinDrug
capreomycin (2nd line TB drug)
moxifloxacinDrug
moxifloxacin (2nd line TB drug)
levoflaxacinDrug
levofloxacin (2nd line TB drug)
ofloxacinDrug
ofloxacin (2nd line TB drug)
ethionamide/prothionamideDrug
ethionamide/prothionamide (2nd line TB drug)
terizidone/cycloserineDrug
terizidone/cycloserine (2nd line TB drug)
para-aminosalicylic acid (PAS)Drug
para-aminosalicylic acid (PAS) (2nd line TB drug)
high dose INHDrug
high dose INH (2nd line TB drug)
bedaquilineDrug
bedaquiline (2nd line TB drug)
clofazamineDrug
clofazamine (2nd TB drug)
delamanidDrug
delamanid (2nd line TB drug)
linezolidDrug
linezolid (2nd line TB drug)
pretomanidDrug
pretomanid (2nd line TB drug)
ethinyl estradiolDrug
oral contraceptives formulated with 30-35 μg ethinyl estradiol
etonogestrel implantDrug
etonogestrel implant contraceptive
nevirapineDrug
nevirapine 200 mg twice a day
amprenavirDrug
amprenavir 1200mg twice a day
abacavirDrug
abacavir 300mg twice a day
lopinavir/ritonavir dosage #2Drug
lopinavir/ritonavir (Kaletra) 400/100mg twice a day
indinavir/ritonavir dosage #1Drug
indinavir/ritonavir 800/100mg twice a day
fosamprenavir/ritonavirDrug
fosamprenavir/ritonavir 700/100 mg twice a day
lopinavir/ritonavir dosage #3Drug
lopinavir/ritonavir (Kaletra) 533/133 mg twice a day
atazanavir/ritonavir dosage #1Drug
atazanavir/ritonavir 300/100 mg once a day
didanosine delayed release (Videx® EC)Drug
didanosine delayed release (Videx® EC) 400 mg once a day if weight > 60 kg; 250 mg once a day if weight < 60 kg
emtricitabineDrug
emtricitabine 200 mg once a day
tenofovirDrug
tenofovir 300 mg once a day
nelfinavir dosage #1Drug
nelfinavir [625 mg tablets] 1250 mg twice a day
tipranavir/ritonavirDrug
tipranavir/ritonavir 500/200 mg twice a day
lopinavir/ritonavir dosage #4Drug
lopinavir/ritonavir (Kaletra) tablets 600/150 mg [3 tablets] twice a day
raltegravirDrug
raltegravir 400 mg twice a day
etravirineDrug
etravirine 200 mg twice a day
maravirocDrug
maraviroc 150 mg or 300 mg twice a day
atazanavir/ritonavir dosage #2Drug
atazanavir/ritonavir 400/100mg once a day
tenofovir/atazanavir/ritonavir dosage #2Drug
tenofovir/atazanavir/ritonavir 300/400/100 mg once a day
nelfinavir dosage #2Drug
nelfinavir [625 mg tablets] 1875 mg twice a day
indinavir/ritonavir dosage #2Drug
indinavir/ritonavir 400/100 mg twice a day
rilpivirineDrug
rilpivirine (25 mg q.d.)
darunavir/ritonavir dosage #4Drug
darunavir/ritonavir once daily 800/100 mg q.d.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: darunavir/ritonavir dosage #1; Drug: darunavir/ritonavir dosage #2; Drug: darunavir/ritonavir dosage #3 | |
| 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.). Receives: Drug: dolutegravir | |
| 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. Receives: Drug: tenofovir alafenamide fumarate (TAF) | |
| 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). Receives: Drug: TAF w/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. Receives: Drug: TAF w/cobicistat or ritonavir | |
| 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 Receives: Drug: elvitegravir/cobicistat | |
| 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. Receives: Drug: darunavir/cobicistat | |
| 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. Receives: Drug: atazanavir/cobicistat | |
| 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) Receives: Drug: efavirenz | |
| 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. Receives: Drug: efavirenz; Drug: rifampicin; Drug: ethambutol; Drug: isoniazid; Drug: pyrazinamide | |
| 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. Receives: Drug: lopinavir/ritonavir dosage #1; Drug: rifampicin; Drug: ethambutol; Drug: isoniazid; Drug: pyrazinamide | |
| 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. Receives: Drug: rifampicin; Drug: ethambutol; Drug: isoniazid; Drug: pyrazinamide | |
| 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 Receives: 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 | |
| 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 Receives: Drug: atazanavir/cobicistat; Drug: darunavir/cobicistat; Drug: 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 Receives: Drug: atazanavir/cobicistat; Drug: darunavir/cobicistat; Drug: etonogestrel implant | |
| 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) Receives: Drug: efavirenz; Drug: 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) Receives: Drug: atazanavir/ritonavir/tenofovir dosage #1; Drug: ethinyl estradiol | |
| NVP 200mg b.i.d | HIV-infected pregnant women ≥ 26 weeks gestation who received nevirapine (NVP) 200 mg twice a day Receives: Drug: nevirapine | |
| APV 1200mg b.i.d | HIV-infected pregnant women ≥ 26 weeks gestation who received amprenavir (APV) 1200mg twice a day Receives: Drug: amprenavir | |
| ABC 300mg b.i.d | HIV-infected pregnant women ≥ 20 weeks gestation who received abacavir (ABC) 300mg twice a day Receives: Drug: abacavir | |
| 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 Receives: Drug: lopinavir/ritonavir dosage #2 | |
| 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 Receives: Drug: indinavir/ritonavir dosage #1 | |
| 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 Receives: Drug: fosamprenavir/ritonavir | |
| 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 Receives: Drug: lopinavir/ritonavir dosage #2; Drug: lopinavir/ritonavir dosage #3 | |
| 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 Receives: Drug: atazanavir/ritonavir dosage #1 | |
| 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 Receives: Drug: didanosine delayed release (Videx® EC) | |
| FTC 200mg q.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received emtricitabine (FTC) 200 mg once a day Receives: Drug: emtricitabine | |
| TFV 300mg q.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir (TFV) 300 mg once a day Receives: Drug: tenofovir | |
| 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 Receives: Drug: atazanavir/ritonavir/tenofovir dosage #1 | |
| 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 Receives: Drug: nelfinavir dosage #1 | |
| EFV 600mg q.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600 mg once a day Receives: Drug: efavirenz | |
| 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 Receives: Drug: tipranavir/ritonavir | |
| 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 Receives: Drug: lopinavir/ritonavir dosage #2; Drug: lopinavir/ritonavir dosage #4 | |
| RAL 400mg b.i.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received raltegravir (RAL) 400 mg twice a day Receives: Drug: raltegravir | |
| ETR 200mg b.i.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received etravirine (ETR) 200mg twice a day Receives: Drug: etravirine | |
| 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 Receives: Drug: maraviroc | |
| 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 Receives: Drug: darunavir/ritonavir dosage #4 | |
| 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 Receives: Drug: darunavir/ritonavir dosage #1 | |
| 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 Receives: Drug: atazanavir/ritonavir dosage #1; Drug: atazanavir/ritonavir dosage #2 | |
| 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 Receives: Drug: atazanavir/ritonavir/tenofovir dosage #1; Drug: tenofovir/atazanavir/ritonavir dosage #2 | |
| 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 Receives: Drug: nelfinavir dosage #1; Drug: nelfinavir dosage #2 | |
| 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 Receives: Drug: indinavir/ritonavir dosage #2 | |
| 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 Receives: Drug: lopinavir/ritonavir dosage #2; Drug: lopinavir/ritonavir dosage #4 | |
| RPV 25mg q.d. | HIV-infected pregnant women ≥ 20 weeks gestation who received rilpivirine (RPV) (25 mg q.d.) Receives: Drug: rilpivirine | |
| 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. Receives: Drug: ethambutol; Drug: isoniazid; Drug: pyrazinamide; Drug: nevirapine | |
| 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 Receives: Drug: atazanavir/ritonavir/tenofovir dosage #1; Drug: etonogestrel implant | |
| 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) Receives: Drug: ethinyl estradiol; Drug: lopinavir/ritonavir dosage #2 | |
| 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 Receives: Drug: etonogestrel implant; Drug: lopinavir/ritonavir dosage #2 | |
| 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 Receives: Drug: efavirenz; Drug: etonogestrel implant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
PK Parameter: Area Under the Curve From 0 to 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: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
PK Parameter: Area Under the Curve From 0 to 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: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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: 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.
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.
The reporting groups for this outcome reflect the drug being analyzed and are therefore not mutually exclusive.
No results are available for LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug arm due to extremely low enrollment.
Measured: 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.
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: Measured at 6-7 weeks after contraceptive initiation postpartum
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: 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.
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: 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 outcomes (4)
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: Measured at time of delivery with single cord blood and single maternal plasma sample.
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: Measured at time of delivery with single cord blood and single maternal plasma sample.
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.
Measured: Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth.
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.
Measured: Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2002 (estimated)
- Study start9 Jun 2003
- Primary completion30 Sep 2020
- Study completion30 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,578 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Mark Mirochnick, MD, Study chair, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00042289
- Sponsor's protocol ID
- P1026s
- Other IDs
- 10040, IMPAACT P1026s
- Status last verified
- Nov 2025
- First submitted
- 26 Jul 2002
- Last updated
- 2 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 14977385Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-87. doi: 10.2165/00003088-200443150-00002.
PubMed 15568888Rakhmanina 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.
PubMed 15228149Sullivan 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.
PubMed 14562860Best 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.
PubMed 16470119Stek 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.
PubMed 16988514Aweeka 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.
PubMed 20002783Mirochnick 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.
PubMed 21283017Capparelli 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.
PubMed 18366444Mirochnick 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.
PubMed 18989231Read 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.
PubMed 18795962Best 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.
PubMed 20632458Stek 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.
PubMed 22129166Cressey 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.
PubMed 22083071Cressey 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.
PubMed 23305215