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NCT Number: NCT00042289

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

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.

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

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

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About this study

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)).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

atazanavir/cobicistat

Drug

atazanavir/cobicistat 300/150 mg q.d.

darunavir/ritonavir dosage #1

Drug

darunavir/ritonavir twice daily 600/100 mg b.i.d.

darunavir/ritonavir dosage #2

Drug

darunavir/ritonavir twice daily 800/100 mg b.i.d.

darunavir/ritonavir dosage #3

Drug

darunavir/ritonavir twice daily 900/100 mg b.i.d.

elvitegravir/cobicistat

Drug

elvitegravir/cobicistat 150/150 mg q.d.

Dolutegravir

Drug

dolutegravir 50 mg q.d.

tenofovir alafenamide fumarate (TAF)

Drug

TAF 25 mg q.d. without cobicistat or ritonavir boosting

TAF w/cobicistat

Drug

TAF 10 mg q.d. with cobicistat

TAF w/cobicistat or ritonavir

Drug

TAF 25 mg q.d. with cobicistat or ritonavir boosting

Efavirenz

Drug

efavirenz 600 mg q.d.

Darunavir/Cobicistat

Drug

darunavir/cobicistat 800/150 mg q.d.

lopinavir/ritonavir dosage #1

Drug

lopinavir/ritonavir 800/200mg b.i.d.

atazanavir/ritonavir/tenofovir dosage #1

Drug

atazanavir/ritonavir/tenofovir 300/100/300mg q.d.

rifampicin

Drug

rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.

Ethambutol

Drug

ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.

Isoniazid

Drug

isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.

Pyrazinamide

Drug

pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.

kanamycin

Drug

kanamycin (2nd line TB drug)

Amikacin

Drug

amikacin (2nd line TB drug)

capreomycin

Drug

capreomycin (2nd line TB drug)

moxifloxacin

Drug

moxifloxacin (2nd line TB drug)

levoflaxacin

Drug

levofloxacin (2nd line TB drug)

Ofloxacin

Drug

ofloxacin (2nd line TB drug)

ethionamide/prothionamide

Drug

ethionamide/prothionamide (2nd line TB drug)

terizidone/cycloserine

Drug

terizidone/cycloserine (2nd line TB drug)

para-aminosalicylic acid (PAS)

Drug

para-aminosalicylic acid (PAS) (2nd line TB drug)

high dose INH

Drug

high dose INH (2nd line TB drug)

Bedaquiline

Drug

bedaquiline (2nd line TB drug)

clofazamine

Drug

clofazamine (2nd TB drug)

Delamanid

Drug

delamanid (2nd line TB drug)

Linezolid

Drug

linezolid (2nd line TB drug)

Pretomanid

Drug

pretomanid (2nd line TB drug)

ethinyl estradiol

Drug

oral contraceptives formulated with 30-35 μg ethinyl estradiol

Etonogestrel implant

Drug

etonogestrel implant contraceptive

Nevirapine

Drug

nevirapine 200 mg twice a day

Amprenavir

Drug

amprenavir 1200mg twice a day

Abacavir

Drug

abacavir 300mg twice a day

lopinavir/ritonavir dosage #2

Drug

lopinavir/ritonavir (Kaletra) 400/100mg twice a day

indinavir/ritonavir dosage #1

Drug

indinavir/ritonavir 800/100mg twice a day

Fosamprenavir/Ritonavir

Drug

fosamprenavir/ritonavir 700/100 mg twice a day

lopinavir/ritonavir dosage #3

Drug

lopinavir/ritonavir (Kaletra) 533/133 mg twice a day

atazanavir/ritonavir dosage #1

Drug

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

Emtricitabine

Drug

emtricitabine 200 mg once a day

Tenofovir

Drug

tenofovir 300 mg once a day

nelfinavir dosage #1

Drug

nelfinavir [625 mg tablets] 1250 mg twice a day

Tipranavir/Ritonavir

Drug

tipranavir/ritonavir 500/200 mg twice a day

lopinavir/ritonavir dosage #4

Drug

lopinavir/ritonavir (Kaletra) tablets 600/150 mg [3 tablets] twice a day

raltegravir

Drug

raltegravir 400 mg twice a day

Etravirine

Drug

etravirine 200 mg twice a day

Maraviroc

Drug

maraviroc 150 mg or 300 mg twice a day

atazanavir/ritonavir dosage #2

Drug

atazanavir/ritonavir 400/100mg once a day

tenofovir/atazanavir/ritonavir dosage #2

Drug

tenofovir/atazanavir/ritonavir 300/400/100 mg once a day

nelfinavir dosage #2

Drug

nelfinavir [625 mg tablets] 1875 mg twice a day

indinavir/ritonavir dosage #2

Drug

indinavir/ritonavir 400/100 mg twice a day

Rilpivirine

Drug

rilpivirine (25 mg q.d.)

darunavir/ritonavir dosage #4

Drug

darunavir/ritonavir once daily 800/100 mg q.d.

Primary outcomes

  1. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.

  2. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs

    Time frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.

  3. PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs

    Time frame: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.

    Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.

  4. PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24 (area under the curve from 0 to 24 hours) were determined using the linear trapezoidal rule.

  5. PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the trapezoidal rule.

  6. PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.

  7. PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.

  8. PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.

  9. PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.

  10. PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.

  11. PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.

  12. PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 12 hrs after an observed dose.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.

  13. PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.

    For the TAF 25 mg q.d., 10 mg q.d. w/COBI, and 25 mg q.d. w/COBI or RTV boosting arms, samples were all below the limit of quantification and statistical analyses were not conducted.

  14. PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.

  15. Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC (area under the curve) were determined using the linear trapezoidal rule. See PK target in the Protocol Appendix V.

  16. Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs

    Time frame: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose. See PK target in Protocol Appendix V.

    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.

  17. Plasma Concentration for Contraceptives

    Time frame: Measured at 6-7 weeks after contraceptive initiation postpartum

    Serum concentrations of the contraceptives. Note that no historical controls were provided by team pharmacologists and thus no comparisons were done for contraceptive concentrations in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.

  18. Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms

    Time frame: Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8 and 12 hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear trapezoidal rule.

  19. Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms

    Time frame: Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8, 12, and 24 hours post dosing.

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the linear trapezoidal rule.

Secondary outcomes

  1. PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs

    Time frame: Measured at time of delivery with single cord blood and single maternal plasma sample.

    Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio.

  2. PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs

    Time frame: Measured at time of delivery with single cord blood and single maternal plasma sample.

    Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio. For arms with zero overall participants analyzed, samples were below the limit of quantification and ratios could not be calculated.

  3. Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs

    Time frame: Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth.

    Infant plasma concentrations were collected and measured during the first 9 days of life. Half-life is defined as 0.693/k, where k, the elimination rate constant, is the slope of the decline in concentrations.

  4. Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs

    Time frame: Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth.

    Infant plasma concentrations were collected and measured during the first 9 days of life.

Other outcomes

  1. ARV Concentrations in Plasma

    Time frame: Measured at intensive PK visit

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belong with Other outcome measures (see SAP).

  2. ARV Concentrations in Vaginal Secretions

    Time frame: Measured at intensive PK visit

    The original study protocol listed this PK parameter under secondary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  3. Drug Parameter: Half-life (t1/2)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  4. Drug Parameter: Volume of Distribution Over Systemic Availability (V/F)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  5. Drug Parameter: Clearance Over Systemic Availability (Cl/F)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  6. Drug Parameter: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  7. Drug Parameter: Minimum Concentration (Cmin)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 weeks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  8. Drug Parameter: Pre-dose Concentration (Cdose)

    Time frame: Measured at intensive PK visit. Timing of intensive PK visit depends on participant's study arm; may occur during 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 wks gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum.

    The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).

  9. Adverse Events of Grade 3 or Higher

    Time frame: Measured through 24 weeks postpartum

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

    See Adverse events section for adverse events.

  10. Infant Neurological Events of Grade 1 or Higher

    Time frame: Measured through 24 weeks of life

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

    See Adverse events section for adverse events.

  11. Adverse Pregnancy Outcome: Preterm Birth

    Time frame: Measured through delivery

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

    See Adverse events section for adverse events.

  12. Adverse Pregnancy Outcome: Low Birth Weight

    Time frame: Measured at delivery

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

    See Adverse events section for adverse events.

  13. Adverse Pregnancy Outcome: Fetal Demise

    Time frame: Measured through 24 weeks postpartum

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

    See Adverse events section for adverse events.

  14. Adverse Pregnancy Outcome: Congenital Anomalies

    Time frame: Measured through 24 weeks of life

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

    See Adverse events section for adverse events.

  15. Infant HIV Infection Status

    Time frame: Measured through 24 weeks of life

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

  16. Ratio of Unbound/Total Drug Concentrations

    Time frame: Measured at time of delivery

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

  17. Rate of Detection of Study Drugs in Vaginal Secretions

    Time frame: Measured at intensive PK visit

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

  18. Ratio of Vaginal Drug Concentrations to Simultaneous Blood Concentrations

    Time frame: Measured at intensive PK visit

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

  19. Rate of Detection of HIV RNA/DNA in Vaginal Secretions and Comparison to Level in Blood

    Time frame: Measured at intensive PK visit

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

  20. ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype

    Time frame: Measured at intensive PK visit

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

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Collaborators

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

Registry information

Official study title

Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum

Important dates

Study start
2003
Primary completion
2020
Study completion
2020
First posted
Aug 1, 2002
Registry last updated
Dec 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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