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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00042289
Recruitment Status : Completed
First Posted : August 1, 2002
Results First Posted : July 22, 2022
Last Update Posted : July 22, 2022
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date July 26, 2002
First Posted Date August 1, 2002
Results First Submitted Date October 5, 2021
Results First Posted Date July 22, 2022
Last Update Posted Date July 22, 2022
Actual Study Start Date June 9, 2003
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 28, 2022)
  • PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
  • PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
  • PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs [ Time Frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing. ]
    Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
  • PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24 (area under the curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
  • PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the trapezoidal rule.
  • PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
  • PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
  • PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
  • PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
  • PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
  • PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
  • PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 12 hrs after an observed dose. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
  • PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose. For the TAF 25 mg q.d., 10 mg q.d. w/COBI, and 25 mg q.d. w/COBI or RTV boosting arms, samples were all below the limit of quantification and statistical analyses were not conducted.
  • PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.
  • Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC (area under the curve) were determined using the linear trapezoidal rule. See PK target in the Protocol Appendix V.
  • Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs [ Time Frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose. See PK target in Protocol Appendix V. No results are available for this outcome measure at this time. The TB drugs are being assayed in batches (not real-time) after the study completion. Labs have been experiencing additional delays due to urgent COVID-19 pandemic related work.
  • Plasma Concentration for Contraceptives [ Time Frame: Measured at 6-7 weeks after contraceptive initiation postpartum ]
    Serum concentrations of the contraceptives. Note that no historical controls were provided by team pharmacologists and thus no comparisons were done for contraceptive concentrations in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.
  • Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms [ Time Frame: Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8 and 12 hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
  • Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms [ Time Frame: Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8, 12, and 24 hours post dosing. ]
    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
Original Primary Outcome Measures
 (submitted: June 23, 2005)
Area under the curve (AUC)
Change History
Current Secondary Outcome Measures
 (submitted: June 28, 2022)
  • PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs [ Time Frame: Measured at time of delivery with single cord blood and single maternal plasma sample. ]
    Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio.
  • PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs [ Time Frame: Measured at time of delivery with single cord blood and single maternal plasma sample. ]
    Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio. For arms with zero overall participants analyzed, samples were below the limit of quantification and ratios could not be calculated.
  • Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs [ Time Frame: Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth. ]
    Infant plasma concentrations were collected and measured during the first 9 days of life. Half-life is defined as 0.693/k, where k, the elimination rate constant, is the slope of the decline in concentrations.
  • Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs [ Time Frame: Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth. ]
    Infant plasma concentrations were collected and measured during the first 9 days of life.
Original Secondary Outcome Measures
 (submitted: June 23, 2005)
  • Ratio of cord blood concentration to maternal blood concentration
  • ratio of 6-beta-hydroxycortisol to cortisol
  • ratio of unbound/total drug concentrations for atazanavir, fosamprenavir, efavirenz, nelfinavir, and tipranavir
Current Other Pre-specified Outcome Measures
 (submitted: June 28, 2022)
  • ARV Concentrations in Plasma [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belong with Other outcome measures (see SAP).
  • ARV Concentrations in Vaginal Secretions [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed this PK parameter under secondary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Half-life (t1/2) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Volume of Distribution Over Systemic Availability (V/F) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Clearance Over Systemic Availability (Cl/F) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Minimum Concentration (Cmin) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Drug Parameter: Pre-dose Concentration (Cdose) [ Time Frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum. ]
    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
  • Adverse Events of Grade 3 or Higher [ Time Frame: Measured through 24 weeks postpartum ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
  • Infant Neurological Events of Grade 1 or Higher [ Time Frame: Measured through 24 weeks of life ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
  • Adverse Pregnancy Outcome: Preterm Birth [ Time Frame: Measured through delivery ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
  • Adverse Pregnancy Outcome: Low Birth Weight [ Time Frame: Measured at delivery ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
  • Adverse Pregnancy Outcome: Fetal Demise [ Time Frame: Measured through 24 weeks postpartum ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
  • Adverse Pregnancy Outcome: Congenital Anomalies [ Time Frame: Measured through 24 weeks of life ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which werenot conducted (see SAP). See Adverse events section for adverse events.
  • Infant HIV Infection Status [ Time Frame: Measured through 24 weeks of life ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
  • Ratio of Unbound/Total Drug Concentrations [ Time Frame: Measured at time of delivery ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
  • Rate of Detection of Study Drugs in Vaginal Secretions [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
  • Ratio of Vaginal Drug Concentrations to Simultaneous Blood Concentrations [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
  • Rate of Detection of HIV RNA/DNA in Vaginal Secretions and Comparison to Level in Blood [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
  • ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype [ Time Frame: Measured at intensive PK visit ]
    The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
Official Title Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
Brief Summary IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs were evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.
Detailed Description

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

P1026s is a Phase IV clinical study. Participants were not assigned to the drugs under study, but were already receiving the drugs for clinical care by prescription of their clinical care providers. They were enrolled into study arms according to the drugs they were receiving through clinical care, and if on multiple drugs of interest, were able to enroll into multiple arms simultaneously. No drugs were provided as part of this study. This observational study was added to an existing investigational new drug (IND) number because several of the drugs were studied at a higher does than the approved dose after the PK results for the approved dose were found to be inadequate.

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

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

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

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

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

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Pregnant and postpartum women from IMPAACT US and non-US sites receiving the medicines specified in the protocol as part of clinical care and infants born to those women enrolled during pregnancy.
Condition HIV Infections
Intervention
  • Drug: atazanavir/cobicistat
    atazanavir/cobicistat 300/150 mg q.d.
  • Drug: darunavir/ritonavir dosage #1
    darunavir/ritonavir twice daily 600/100 mg b.i.d.
  • Drug: darunavir/ritonavir dosage #2
    darunavir/ritonavir twice daily 800/100 mg b.i.d.
  • Drug: darunavir/ritonavir dosage #3
    darunavir/ritonavir twice daily 900/100 mg b.i.d.
  • Drug: elvitegravir/cobicistat
    elvitegravir/cobicistat 150/150 mg q.d.
  • Drug: dolutegravir
    dolutegravir 50 mg q.d.
  • Drug: tenofovir alafenamide fumarate (TAF)
    TAF 25 mg q.d. without cobicistat or ritonavir boosting
  • Drug: TAF w/cobicistat
    TAF 10 mg q.d. with cobicistat
  • Drug: TAF w/cobicistat or ritonavir
    TAF 25 mg q.d. with cobicistat or ritonavir boosting
  • Drug: efavirenz
    efavirenz 600 mg q.d.
  • Drug: darunavir/cobicistat
    darunavir/cobicistat 800/150 mg q.d.
  • Drug: lopinavir/ritonavir dosage #1
    lopinavir/ritonavir 800/200mg b.i.d.
  • Drug: atazanavir/ritonavir/tenofovir dosage #1
    atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
  • Drug: rifampicin
    rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
  • Drug: ethambutol
    ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
  • Drug: isoniazid
    isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
  • Drug: pyrazinamide
    pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
  • Drug: kanamycin
    kanamycin (2nd line TB drug)
  • Drug: amikacin
    amikacin (2nd line TB drug)
  • Drug: capreomycin
    capreomycin (2nd line TB drug)
  • Drug: moxifloxacin
    moxifloxacin (2nd line TB drug)
  • Drug: levoflaxacin
    levofloxacin (2nd line TB drug)
  • Drug: ofloxacin
    ofloxacin (2nd line TB drug)
  • Drug: ethionamide/prothionamide
    ethionamide/prothionamide (2nd line TB drug)
  • Drug: terizidone/cycloserine
    terizidone/cycloserine (2nd line TB drug)
  • Drug: para-aminosalicylic acid (PAS)
    para-aminosalicylic acid (PAS) (2nd line TB drug)
  • Drug: high dose INH
    high dose INH (2nd line TB drug)
  • Drug: bedaquiline
    bedaquiline (2nd line TB drug)
  • Drug: clofazamine
    clofazamine (2nd TB drug)
  • Drug: delamanid
    delamanid (2nd line TB drug)
  • Drug: linezolid
    linezolid (2nd line TB drug)
  • Drug: pretomanid
    pretomanid (2nd line TB drug)
  • Drug: ethinyl estradiol
    oral contraceptives formulated with 30-35 μg ethinyl estradiol
  • Drug: etonogestrel implant
    etonogestrel implant contraceptive
  • Drug: nevirapine
    nevirapine 200 mg twice a day
  • Drug: amprenavir
    amprenavir 1200mg twice a day
  • Drug: abacavir
    abacavir 300mg twice a day
  • Drug: lopinavir/ritonavir dosage #2
    lopinavir/ritonavir (Kaletra) 400/100mg twice a day
  • Drug: indinavir/ritonavir dosage #1
    indinavir/ritonavir 800/100mg twice a day
  • Drug: fosamprenavir/ritonavir
    fosamprenavir/ritonavir 700/100 mg twice a day
  • Drug: lopinavir/ritonavir dosage #3
    lopinavir/ritonavir (Kaletra) 533/133 mg twice a day
  • Drug: atazanavir/ritonavir dosage #1
    atazanavir/ritonavir 300/100 mg once a day
  • Drug: didanosine delayed release (Videx® EC)
    didanosine delayed release (Videx® EC) 400 mg once a day if weight > 60 kg; 250 mg once a day if weight < 60 kg
  • Drug: emtricitabine
    emtricitabine 200 mg once a day
  • Drug: tenofovir
    tenofovir 300 mg once a day
  • Drug: nelfinavir dosage #1
    nelfinavir [625 mg tablets] 1250 mg twice a day
  • Drug: tipranavir/ritonavir
    tipranavir/ritonavir 500/200 mg twice a day
  • Drug: lopinavir/ritonavir dosage #4
    lopinavir/ritonavir (Kaletra) tablets 600/150 mg [3 tablets] twice a day
  • Drug: raltegravir
    raltegravir 400 mg twice a day
  • Drug: etravirine
    etravirine 200 mg twice a day
  • Drug: maraviroc
    maraviroc 150 mg or 300 mg twice a day
  • Drug: atazanavir/ritonavir dosage #2
    atazanavir/ritonavir 400/100mg once a day
  • Drug: tenofovir/atazanavir/ritonavir dosage #2
    tenofovir/atazanavir/ritonavir 300/400/100 mg once a day
  • Drug: nelfinavir dosage #2
    nelfinavir [625 mg tablets] 1875 mg twice a day
  • Drug: indinavir/ritonavir dosage #2
    indinavir/ritonavir 400/100 mg twice a day
  • Drug: rilpivirine
    rilpivirine (25 mg q.d.)
  • Drug: darunavir/ritonavir dosage #4
    darunavir/ritonavir once daily 800/100 mg q.d.
Study Groups/Cohorts
  • 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.

    Interventions:
    • 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.).
    Intervention: 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.
    Intervention: 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).
    Intervention: 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.
    Intervention: 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
    Intervention: 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.
    Intervention: 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.
    Intervention: 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)
    Intervention: 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.
    Interventions:
    • 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.
    Interventions:
    • 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.
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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)
    Interventions:
    • 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)
    Interventions:
    • 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
    Intervention: Drug: nevirapine
  • APV 1200mg b.i.d
    HIV-infected pregnant women ≥ 26 weeks gestation who received amprenavir (APV) 1200mg twice a day
    Intervention: Drug: amprenavir
  • ABC 300mg b.i.d
    HIV-infected pregnant women ≥ 20 weeks gestation who received abacavir (ABC) 300mg twice a day
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Interventions:
    • 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
    Intervention: 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
    Intervention: 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
    Intervention: Drug: emtricitabine
  • TFV 300mg q.d.
    HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir (TFV) 300 mg once a day
    Intervention: 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
    Intervention: 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
    Intervention: Drug: nelfinavir dosage #1
  • EFV 600mg q.d.
    HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600 mg once a day
    Intervention: 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
    Intervention: 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
    Interventions:
    • 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
    Intervention: Drug: raltegravir
  • ETR 200mg b.i.d.
    HIV-infected pregnant women ≥ 20 weeks gestation who received etravirine (ETR) 200mg twice a day
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Intervention: 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
    Interventions:
    • 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.)
    Intervention: 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.
    Interventions:
    • 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
    Interventions:
    • 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)
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • Drug: efavirenz
    • Drug: etonogestrel implant
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 10, 2020)
1578
Original Enrollment
 (submitted: June 23, 2005)
125
Actual Study Completion Date September 30, 2020
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Maternal Inclusion Criteria:

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

    1. HIV-infected pregnant women greater than or equal to 20 weeks gestation NOT on TB treatment receiving one or more of the ARV drugs/drug combinations specified in the protocol
    2. HIV-infected pregnant women greater than or equal to 20 weeks gestation receiving one of the ARV drugs/drug combinations specified in the protocol and TB treatment with at least one of the TB drugs, specified in the protocol, at study entry
    3. HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the first-line TB drugs, specified in the protocol, at study entry
    4. HIV-infected and HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the second-line TB drugs, specified in the protocol, at study entry
    5. HIV-infected women 2 to 12 weeks (14 to 84 days) post-delivery receiving one of the ARV drug combinations listed in the protocol AND starting postpartum contraceptives as listed in the protocol
  • The woman must be stable on the ARV drug/drug combination and/or TB drug combination for at least 2 weeks prior to PK sampling
  • If a woman is receiving a specific generic ARV formulation, the protocol team has approved this formulation
  • HIV-infected pregnant women must be planning to continue on current ARV regimen until postpartum PK sampling is completed. HIV-infected postpartum women on hormonal contraceptives must be planning to continue on ARV and contraceptive regimens until final PK sampling is completed
  • For HIV-infected women: confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry. More information on this criterion can be found in the protocol.
  • HIV-uninfected pregnant women must have documented negative HIV antibody test during current pregnancy. Note: adequate source documentation, including the date of specimen collection, date of testing, test performed, and test result, must be available.
  • Participants enrolling in the 3rd trimester must enroll by 37 6/7 weeks gestation
  • Participant can provide legal informed consent per local regulations
  • If a woman has completed this study and becomes pregnant again, she may re-enroll in the study only if she is enrolled in a different arm than that studied during her initial enrollment

Maternal Exclusion Criteria:

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

Infant Enrollment Criteria:

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

Infant Requirements for Washout Pharmacokinetic Sampling:

  • Born to HIV-infected mother enrolled during pregnancy in an ARV arm (does not include infants born to HIV-uninfected mothers receiving TB drugs)
  • Birth weight greater than 1000 grams
  • Is NOT receiving disallowed medications described in Section 7 of the protocol
  • Does not have any severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the site investigator
  • Born after singleton delivery (not after multiple birth)
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Argentina,   Botswana,   Brazil,   Puerto Rico,   South Africa,   Tanzania,   Thailand,   United States
Removed Location Countries Uganda
 
Administrative Information
NCT Number NCT00042289
Other Study ID Numbers P1026s
10040 ( Registry Identifier: DAIDS ES )
IMPAACT P1026s
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Not Provided
Current Study Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor Same as current
Collaborators Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Chair: Mark Mirochnick, MD Boston Medical Center
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date June 2022