HIV Infections
Conditions
Keywords
Pregnancy, Pharmacokinetics, Treatment Experienced
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)).
Interventions
DRUGlevoflaxacin
levofloxacin (2nd line TB drug)
DRUGofloxacin
ofloxacin (2nd line TB drug)
DRUGethionamide/prothionamide
ethionamide/prothionamide (2nd line TB drug)
DRUGamikacin
amikacin (2nd line TB drug)
DRUGcapreomycin
capreomycin (2nd line TB drug)
DRUGmoxifloxacin
moxifloxacin (2nd line TB drug)
atazanavir/cobicistat 300/150 mg q.d.
DRUGdarunavir/ritonavir dosage #1
darunavir/ritonavir twice daily 600/100 mg b.i.d.
DRUGdarunavir/ritonavir dosage #2
darunavir/ritonavir twice daily 800/100 mg b.i.d.
DRUGdarunavir/ritonavir dosage #3
darunavir/ritonavir twice daily 900/100 mg b.i.d.
DRUGelvitegravir/cobicistat
elvitegravir/cobicistat 150/150 mg q.d.
DRUGdolutegravir
dolutegravir 50 mg q.d.
TAF 25 mg q.d. without cobicistat or ritonavir boosting
DRUGTAF w/cobicistat
TAF 10 mg q.d. with cobicistat
DRUGTAF w/cobicistat or ritonavir
TAF 25 mg q.d. with cobicistat or ritonavir boosting
DRUGefavirenz
efavirenz 600 mg q.d.
darunavir/cobicistat 800/150 mg q.d.
DRUGlopinavir/ritonavir dosage #1
lopinavir/ritonavir 800/200mg b.i.d.
DRUGatazanavir/ritonavir/tenofovir dosage #1
atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
DRUGrifampicin
rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
DRUGethambutol
ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
DRUGisoniazid
isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
DRUGpyrazinamide
pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
DRUGkanamycin
kanamycin (2nd line TB drug)
DRUGterizidone/cycloserine
terizidone/cycloserine (2nd line TB drug)
DRUGpara-aminosalicylic acid (PAS)
para-aminosalicylic acid (PAS) (2nd line TB drug)
DRUGhigh dose INH
high dose INH (2nd line TB drug)
DRUGbedaquiline
bedaquiline (2nd line TB drug)
DRUGclofazamine
clofazamine (2nd TB drug)
DRUGdelamanid
delamanid (2nd line TB drug)
DRUGlinezolid
linezolid (2nd line TB drug)
DRUGpretomanid
pretomanid (2nd line TB drug)
oral contraceptives formulated with 30-35 μg ethinyl estradiol
etonogestrel implant contraceptive
DRUGnevirapine
nevirapine 200 mg twice a day
DRUGamprenavir
amprenavir 1200mg twice a day
DRUGabacavir
abacavir 300mg twice a day
DRUGlopinavir/ritonavir dosage #2
lopinavir/ritonavir (Kaletra) 400/100mg twice a day
DRUGindinavir/ritonavir dosage #1
indinavir/ritonavir 800/100mg twice a day
fosamprenavir/ritonavir 700/100 mg twice a day
DRUGlopinavir/ritonavir dosage #3
lopinavir/ritonavir (Kaletra) 533/133 mg twice a day
DRUGatazanavir/ritonavir dosage #1
atazanavir/ritonavir 300/100 mg once a day
DRUGdidanosine 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
DRUGemtricitabine
emtricitabine 200 mg once a day
DRUGtenofovir
tenofovir 300 mg once a day
DRUGnelfinavir dosage #1
nelfinavir \[625 mg tablets\] 1250 mg twice a day
tipranavir/ritonavir 500/200 mg twice a day
DRUGlopinavir/ritonavir dosage #4
lopinavir/ritonavir (Kaletra) tablets 600/150 mg \[3 tablets\] twice a day
DRUGraltegravir
raltegravir 400 mg twice a day
DRUGetravirine
etravirine 200 mg twice a day
DRUGmaraviroc
maraviroc 150 mg or 300 mg twice a day
DRUGatazanavir/ritonavir dosage #2
atazanavir/ritonavir 400/100mg once a day
DRUGtenofovir/atazanavir/ritonavir dosage #2
tenofovir/atazanavir/ritonavir 300/400/100 mg once a day
DRUGnelfinavir dosage #2
nelfinavir \[625 mg tablets\] 1875 mg twice a day
DRUGindinavir/ritonavir dosage #2
indinavir/ritonavir 400/100 mg twice a day
DRUGrilpivirine
rilpivirine (25 mg q.d.)
DRUGdarunavir/ritonavir dosage #4
darunavir/ritonavir once daily 800/100 mg q.d.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) 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. | 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. |
| Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms | 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. |
| Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms | 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. |
| Plasma Concentration for Contraceptives | 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. |
| Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 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. |
| Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 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. |
| PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | 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. |
| PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 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 (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs | 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 (C12) With Median (Range) for ARVs and TB Drugs | 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 (IQR) for ARVs and TB Drugs | 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: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs | 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 | 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 | 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 (IQR) for ARVs and TB Drugs | 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: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | 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: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 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 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs | Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing. | Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing. |
| PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 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. |
| PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 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. |
| Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| ARV Concentrations in Vaginal Secretions | 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). |
| ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype | 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 | 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 | 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 Study Drugs in Vaginal Secretions | 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 Unbound/Total Drug Concentrations | 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). |
| Infant HIV Infection Status | 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). |
| Adverse Pregnancy Outcome: Congenital Anomalies | 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. |
| Adverse Pregnancy Outcome: Fetal Demise | 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: Low Birth Weight | 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: Preterm Birth | 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. |
| Infant Neurological Events of Grade 1 or Higher | 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 Events of Grade 3 or Higher | 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. |
| Drug Parameter: Pre-dose Concentration (Cdose) | 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) | 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: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax) | 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: Clearance Over Systemic Availability (Cl/F) | 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) | 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). |
| ARV Concentrations in Plasma | 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). |
| Drug Parameter: Half-life (t1/2) | 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). |
Countries
Argentina, Botswana, Brazil, Puerto Rico, South Africa, Tanzania, Thailand, United States
Participant flow
Recruitment details
Participants enrolled between 9Jun2003 and 30Dec2019 at US and non-US clinical research sites and could enroll in multiple arms, simultaneously; thus, reporting groups are not mutually exclusive and totals do not reflect the number of unique participants. There were 1578 unique participants (1037 mothers and 541 infants), including 8 mothers enrolled in 3 arms, 36 mothers enrolled in 2 arms, and 24 mother-infant pairs enrolled in 2 arms. Each arm was designed as a separate single-arm evaluation.
Participants by arm
| Arm | Count |
|---|---|
| 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 twice daily 600/100 mg 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.
darunavir/ritonavir dosage #1: darunavir/ritonavir twice daily 600/100 mg b.i.d.
darunavir/ritonavir dosage #2: darunavir/ritonavir twice daily 800/100 mg b.i.d.
darunavir/ritonavir dosage #3: darunavir/ritonavir twice daily 900/100 mg b.i.d. | 26 |
| DTG 50mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received dolutegravir 50 mg q.d.
dolutegravir: dolutegravir 50 mg q.d. | 30 |
| 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.
tenofovir alafenamide fumarate (TAF): TAF 25 mg q.d. without cobicistat or ritonavir boosting | 27 |
| 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.
TAF w/cobicistat: TAF 10 mg q.d. with cobicistat | 33 |
| 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 or ritonavir boosting.
TAF w/cobicistat or ritonavir: TAF 25 mg q.d. with cobicistat or ritonavir boosting | 29 |
| EVG/COBI 150/150mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received elvitegravir/cobicistat 150/150 mg q.d
elvitegravir/cobicistat: elvitegravir/cobicistat 150/150 mg q.d. | 31 |
| DRV/COBI 800/150 mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received darunavir/cobicistat 800/150 mg q.d.
darunavir/cobicistat: darunavir/cobicistat 800/150 mg q.d. | 28 |
| ATV/COBI 300/150 mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received atazanavir/cobicistat 300/150 mg q.d.
atazanavir/cobicistat: atazanavir/cobicistat 300/150 mg q.d. | 12 |
| EFV 600 mg q.d. (Outside THA) HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received efavirenz 600 mg q.d. (Participants outside of Thailand only)
efavirenz: efavirenz 600 mg q.d. | 27 |
| EFV 600mg q.d. and at Least One 1st Line TB Drug HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz 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.
efavirenz: efavirenz 600 mg q.d.
rifampicin: rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
ethambutol: ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
isoniazid: isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
pyrazinamide: pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w. | 24 |
| 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 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.
lopinavir/ritonavir dosage #1: lopinavir/ritonavir 800/200mg b.i.d.
rifampicin: rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
ethambutol: ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
isoniazid: isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
pyrazinamide: pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w. | 2 |
| 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.
rifampicin: rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
ethambutol: ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
isoniazid: isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
pyrazinamide: pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w. | 27 |
| 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
kanamycin: kanamycin (2nd line TB drug)
amikacin: amikacin (2nd line TB drug)
capreomycin: capreomycin (2nd line TB drug)
moxifloxacin: moxifloxacin (2nd line TB drug)
levoflaxacin: levofloxacin (2nd line TB drug)
ofloxacin: ofloxacin (2nd line TB drug)
ethionamide/prothionamide: ethionamide/prothionamide (2nd line TB drug)
terizidone/cycloserine: terizidone/cycloserine (2nd line TB drug)
para-aminosalicylic acid (PAS): para-aminosalicylic acid (PAS) (2nd line TB drug)
high dose INH: high dose INH (2nd line TB drug)
bedaquiline: bedaquiline (2nd line TB drug)
clofazamine: clofazamine (2nd TB drug)
delamanid: delamanid (2nd line TB drug)
linezolid: linezolid (2nd line TB drug)
pretomanid: pretomanid (2nd line TB drug) | 13 |
| 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 800/150 mg q.d. or atazanavir/cobicistat 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
atazanavir/cobicistat: atazanavir/cobicistat 300/150 mg q.d.
darunavir/cobicistat: darunavir/cobicistat 800/150 mg q.d.
ethinyl estradiol: oral contraceptives formulated with 30-35 μg ethinyl estradiol | 2 |
| 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 800/150 mg q.d. or atazanavir/cobicistat 300/150 mg q.d. postpartum and starting etonogestrel implant
atazanavir/cobicistat: atazanavir/cobicistat 300/150 mg q.d.
darunavir/cobicistat: darunavir/cobicistat 800/150 mg q.d.
etonogestrel implant: etonogestrel implant contraceptive | 6 |
| EFV 600mg q.d. With 30-35ug EE HIV-infected women 2-12 weeks (14-84 days) post-delivery who received efavirenz 600mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
efavirenz: efavirenz 600 mg q.d.
ethinyl estradiol: oral contraceptives formulated with 30-35 μg ethinyl estradiol | 29 |
| 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 300/100/300 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
atazanavir/ritonavir/tenofovir dosage #1: atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
ethinyl estradiol: oral contraceptives formulated with 30-35 μg ethinyl estradiol | 28 |
| NVP 200mg b.i.d HIV-infected pregnant women ≥ 26 weeks gestation who received nevirapine 200 mg twice a day
nevirapine: nevirapine 200 mg twice a day | 12 |
| ABC 300mg b.i.d HIV-infected pregnant women ≥ 20 weeks gestation who received abacavir 300mg twice a day
abacavir: abacavir 300mg twice a day | 26 |
| LPV/RTV Arm 1: 400/100mg b.i.d HIV-infected pregnant women ≥ 26 weeks gestation who received lopinavir/ritonavir (Kaletra) 400/100mg twice a day
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day | 17 |
| IDV/RTV Arm 1: 800/100mg b.i.d HIV-infected pregnant women ≥ 26 weeks gestation who received indinavir/ritonavir 800/100 mg twice a day
indinavir/ritonavir dosage #1: indinavir/ritonavir 800/100mg twice a day | 1 |
| FPV/RTV 700/100mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received fosamprenavir/ritonavir 700/100mg twice a day
fosamprenavir/ritonavir: fosamprenavir/ritonavir 700/100 mg twice a day | 30 |
| 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 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
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day
lopinavir/ritonavir dosage #3: lopinavir/ritonavir (Kaletra) 533/133 mg twice a day | 29 |
| ATV/RTV Arm 1: 300/100mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir 300/100 mg once a day
atazanavir/ritonavir dosage #1: atazanavir/ritonavir 300/100 mg once a day | 22 |
| DDI 400mg or 250mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received didanosine delayed release (Videx® EC) 400 mg once a day if weight \> 60 kg; 250 mg once a day if weight \< 60 kg
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 | 18 |
| FTC 200mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received emtricitabine 200 mg once a day
emtricitabine: emtricitabine 200 mg once a day | 21 |
| TFV 300mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir 300 mg once a day
tenofovir: tenofovir 300 mg once a day | 28 |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir 300/300/100 mg once a day
atazanavir/ritonavir/tenofovir dosage #1: atazanavir/ritonavir/tenofovir 300/100/300mg q.d. | 25 |
| NFV Arm 1: 1250mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir \[625 mg tablets\] 1250 mg twice a day
nelfinavir dosage #1: nelfinavir \[625 mg tablets\] 1250 mg twice a day | 29 |
| EFV 600mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz 600 mg once a day
efavirenz: efavirenz 600 mg q.d. | 25 |
| TPV/RTV 500/200mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received tipranavir/ritonavir 500/200 mg twice a day
tipranavir/ritonavir: tipranavir/ritonavir 500/200 mg twice a day | 1 |
| 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 (Kaletra) 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
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day
lopinavir/ritonavir dosage #4: lopinavir/ritonavir (Kaletra) tablets 600/150 mg \[3 tablets\] twice a day | 35 |
| RAL 400mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received raltegravir 400 mg twice a day
raltegravir: raltegravir 400 mg twice a day | 43 |
| ETR 200mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received etravirine 200mg twice a day
etravirine: etravirine 200 mg twice a day | 16 |
| MVC 150 or 300mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received maraviroc 150 mg or 300 mg twice a day
maraviroc: maraviroc 150 mg or 300 mg twice a day | 12 |
| DRV/RTV 800/100mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir 800/100 mg once a day
darunavir/ritonavir dosage #4: darunavir/ritonavir once daily 800/100 mg q.d. | 32 |
| DRV/RTV 600/100mg b.i.d. HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir 600/100 mg twice a day
darunavir/ritonavir dosage #1: darunavir/ritonavir twice daily 600/100 mg b.i.d. | 36 |
| 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 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
atazanavir/ritonavir dosage #1: atazanavir/ritonavir 300/100 mg once a day
atazanavir/ritonavir dosage #2: atazanavir/ritonavir 400/100mg once a day | 38 |
| 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 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
atazanavir/ritonavir/tenofovir dosage #1: atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
tenofovir/atazanavir/ritonavir dosage #2: tenofovir/atazanavir/ritonavir 300/400/100 mg once a day | 35 |
| 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 \[625 mg tablets\] 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
nelfinavir dosage #1: nelfinavir \[625 mg tablets\] 1250 mg twice a day
nelfinavir dosage #2: nelfinavir \[625 mg tablets\] 1875 mg twice a day | 18 |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) HIV-infected pregnant women ≥ 20 weeks gestation who received indinavir/ritonavir 400/100 mg twice a day only to participants enrolling in Thailand
indinavir/ritonavir dosage #2: indinavir/ritonavir 400/100 mg twice a day | 26 |
| 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 (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
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day
lopinavir/ritonavir dosage #4: lopinavir/ritonavir (Kaletra) tablets 600/150 mg \[3 tablets\] twice a day | 25 |
| RPV 25mg q.d. HIV-infected pregnant women ≥ 20 weeks gestation who received rilpivirine (25 mg q.d.)
rilpivirine: rilpivirine (25 mg q.d.) | 32 |
| ATV/RTV/TFV 300/100/300mg q.d. With ENG HIV- infected women 2-12 weeks postpartum who received atazanavir/ritonavir/tenofovir 300/100/300 mg q.d. postpartum and starting postpartum etonogestrel implant
atazanavir/ritonavir/tenofovir dosage #1: atazanavir/ritonavir/tenofovir 300/100/300mg q.d.
etonogestrel implant: etonogestrel implant contraceptive | 25 |
| LPV/RTV 400/100 b.i.d. With 30-35ug EE HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir 400/100 b.i.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
ethinyl estradiol: oral contraceptives formulated with 30-35 μg ethinyl estradiol
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day | 27 |
| LPV/RTV 400/100 b.i.d. With ENG HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir 400/100 b.i.d. postpartum and starting postpartum etonogestrel implant
etonogestrel implant: etonogestrel implant contraceptive
lopinavir/ritonavir dosage #2: lopinavir/ritonavir (Kaletra) 400/100mg twice a day | 27 |
| EFV 600mg q.d. With ENG HIV-infected women 2-12 weeks postpartum who received efavirenz 600mg q.d. postpartum and starting postpartum etonogestrel implant
efavirenz: efavirenz 600 mg q.d.
etonogestrel implant: etonogestrel implant contraceptive | 28 |
| Total | 1,113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 | FG028 | FG029 | FG030 | FG031 | FG032 | FG033 | FG034 | FG035 | FG036 | FG037 | FG038 | FG039 | FG040 | FG041 | FG042 | FG043 | FG044 | FG045 | FG046 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 1 | 3 | 3 | 6 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 0 | 0 | 2 | 1 | 1 | 1 | 2 | 1 | 1 | 0 | 5 | 0 | 2 | 2 | 0 | 0 | 1 | 0 |
| Overall Study | Other reason | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Participant not willing to adhere to requirements | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 0 | 2 | 1 | 1 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 1 | 1 | 3 | 1 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Severe debilitation, unable to continue | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Site closed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | DTG 50mg q.d. | TAF 25mg q.d. | TAF 10mg q.d. w/COBI | TAF 25mg q.d. w/COBI or RTV Boosting | EVG/COBI 150/150mg q.d. | DRV/COBI 800/150 mg q.d. | ATV/COBI 300/150 mg q.d. | EFV 600 mg q.d. (Outside THA) | EFV 600mg q.d. and at Least One 1st Line TB Drug | No ARVs and at Least Two 1st Line TB Drugs | At Least Two 2nd Line TB Drugs w/ or w/Out ARVs | DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d With ENG | EFV 600mg q.d. With 30-35ug EE | ATV/RTV/TFV 300/100/300mg q.d. With 30-35ug EE | NVP 200mg b.i.d | ABC 300mg b.i.d | LPV/RTV Arm 1: 400/100mg b.i.d | FPV/RTV 700/100mg b.i.d. | LPV/RTV Arm 2: 400/100mg b.i.d. Then 533/133mg b.i.d. | ATV/RTV Arm 1: 300/100mg q.d. | DDI 400mg or 250mg q.d. | FTC 200mg q.d. | 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. | TFV 300mg q.d. | TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | NFV Arm 1: 1250mg b.i.d. | EFV 600mg q.d. | LPV/RTV Arm 3: 400/100mg b.i.d. Then 600/150mg b.i.d. Then 400/100mg b.i.d. | RAL 400mg b.i.d. | ETR 200mg b.i.d. | MVC 150 or 300mg b.i.d. | DRV/RTV 800/100mg q.d. | DRV/RTV 600/100mg b.i.d. | ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | LPV/RTV Arm 4: 400/100mg b.i.d. Then 600/150mg b.i.d. Then 400/100mg b.i.d. (Only African Sites) | RPV 25mg q.d. | ATV/RTV/TFV 300/100/300mg q.d. With ENG | LPV/RTV 400/100 b.i.d. With 30-35ug EE | LPV/RTV 400/100 b.i.d. With ENG | EFV 600mg q.d. With ENG | Total | TPV/RTV 500/200mg b.i.d. | IDV/RTV Arm 1: 800/100mg b.i.d | DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d With 30-35ug EE | LPV/RTV 800/200mg b.i.d. and at Least One 1st Line TB Drug |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.8 years | 29.3 years | 33.6 years | 30.8 years | 32.1 years | 27.7 years | 33.1 years | 30.6 years | 31.4 years | 25.9 years | 32.5 years | 33.2 years | 27.1 years | 32.0 years | 29.5 years | 28.4 years | 31.4 years | 30.7 years | 31.8 years | 31.1 years | 28.7 years | 29.6 years | 28.8 years | 30.2 years | 31.0 years | 28.7 years | 29.3 years | 30.4 years | 30.5 years | 25.5 years | 23.8 years | 27.6 years | 27.0 years | 31.0 years | 26.9 years | 28.6 years | 30.4 years | 29.0 years | 26.7 years | 26.9 years | 29.4 years | 26.9 years | 24.3 years | 29.4 years | — | — | — | — |
| Race/Ethnicity, Customized American Indian, Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | — | — | — | — |
| Race/Ethnicity, Customized Asian, Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 9 Participants | 0 Participants | 0 Participants | 12 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 21 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 17 Participants | 0 Participants | 0 Participants | 26 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 112 Participants | — | — | — | — |
| Race/Ethnicity, Customized Black Non-Hispanic | 21 Participants | 8 Participants | 20 Participants | 14 Participants | 22 Participants | 18 Participants | 6 Participants | 12 Participants | 21 Participants | 14 Participants | 12 Participants | 3 Participants | 1 Participants | 6 Participants | 5 Participants | 14 Participants | 7 Participants | 13 Participants | 10 Participants | 14 Participants | 5 Participants | 6 Participants | 13 Participants | 9 Participants | 12 Participants | 17 Participants | 1 Participants | 7 Participants | 21 Participants | 7 Participants | 4 Participants | 18 Participants | 12 Participants | 5 Participants | 15 Participants | 10 Participants | 0 Participants | 25 Participants | 18 Participants | 6 Participants | 3 Participants | 1 Participants | 0 Participants | 456 Participants | — | — | — | — |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 4 Participants | 14 Participants | 10 Participants | 13 Participants | 5 Participants | 10 Participants | 2 Participants | 15 Participants | 1 Participants | 4 Participants | 0 Participants | 3 Participants | 16 Participants | 20 Participants | 4 Participants | 7 Participants | 7 Participants | 15 Participants | 11 Participants | 7 Participants | 11 Participants | 7 Participants | 12 Participants | 10 Participants | 7 Participants | 11 Participants | 2 Participants | 22 Participants | 18 Participants | 9 Participants | 7 Participants | 11 Participants | 15 Participants | 16 Participants | 16 Participants | 6 Participants | 0 Participants | 0 Participants | 12 Participants | 19 Participants | 24 Participants | 26 Participants | 20 Participants | 449 Participants | — | — | — | — |
| Race/Ethnicity, Customized More Than One Race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | — | — | — | — |
| Race/Ethnicity, Customized White Non-Hispanic | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 7 Participants | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 8 Participants | 4 Participants | 1 Participants | 0 Participants | 6 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 74 Participants | — | — | — | — |
| Sex: Female, Male Female | 30 Participants | 27 Participants | 33 Participants | 29 Participants | 31 Participants | 28 Participants | 12 Participants | 27 Participants | 24 Participants | 27 Participants | 13 Participants | 6 Participants | 29 Participants | 28 Participants | 12 Participants | 26 Participants | 17 Participants | 30 Participants | 29 Participants | 22 Participants | 18 Participants | 21 Participants | 26 Participants | 28 Participants | 25 Participants | 29 Participants | 25 Participants | 35 Participants | 43 Participants | 16 Participants | 12 Participants | 32 Participants | 36 Participants | 38 Participants | 35 Participants | 18 Participants | 26 Participants | 25 Participants | 32 Participants | 25 Participants | 27 Participants | 27 Participants | 28 Participants | 1113 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk | EG033 affected / at risk | EG034 affected / at risk | EG035 affected / at risk | EG036 affected / at risk | EG037 affected / at risk | EG038 affected / at risk | EG039 affected / at risk | EG040 affected / at risk | EG041 affected / at risk | EG042 affected / at risk | EG043 affected / at risk | EG044 affected / at risk | EG045 affected / at risk | EG046 affected / at risk | EG047 affected / at risk | EG048 affected / at risk | EG049 affected / at risk | EG050 affected / at risk | EG051 affected / at risk | EG052 affected / at risk | EG053 affected / at risk | EG054 affected / at risk | EG055 affected / at risk | EG056 affected / at risk | EG057 affected / at risk | EG058 affected / at risk | EG059 affected / at risk | EG060 affected / at risk | EG061 affected / at risk | EG062 affected / at risk | EG063 affected / at risk | EG064 affected / at risk | EG065 affected / at risk | EG066 affected / at risk | EG067 affected / at risk | EG068 affected / at risk | EG069 affected / at risk | EG070 affected / at risk | EG071 affected / at risk | EG072 affected / at risk | EG073 affected / at risk | EG074 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 12 | 0 / 12 | 0 / 22 | 0 / 22 | 0 / 38 | 0 / 38 | 0 / 28 | 0 / 25 | 0 / 14 | 0 / 13 | 0 / 4 | 0 / 18 | 0 / 27 | 0 / 28 | 0 / 2 | 0 / 6 | 0 / 25 | 0 / 26 | 1 / 9 | 0 / 36 | 0 / 32 | 0 / 30 | 0 / 30 | 0 / 26 | 0 / 27 | 0 / 21 | 0 / 25 | 1 / 23 | 0 / 24 | 0 / 29 | 0 / 28 | 0 / 6 | 0 / 16 | 0 / 31 | 0 / 31 | 0 / 9 | 0 / 30 | 0 / 5 | 0 / 21 | 0 / 26 | 0 / 26 | 0 / 1 | 0 / 27 | 0 / 27 | 0 / 17 | 0 / 29 | 1 / 25 | 0 / 25 | 0 / 35 | 0 / 2 | 0 / 2 | 0 / 4 | 0 / 12 | 0 / 29 | 0 / 18 | 0 / 12 | 2 / 27 | 0 / 27 | 0 / 6 | 0 / 43 | 0 / 30 | 0 / 32 | 0 / 32 | 0 / 33 | 0 / 27 | 0 / 27 | 0 / 28 | 0 / 29 | 0 / 28 | 0 / 21 | 0 / 25 | 0 / 35 | 0 / 35 | 0 / 1 |
| other Total, other adverse events | 21 / 26 | 9 / 12 | 11 / 12 | 8 / 22 | 21 / 22 | 23 / 38 | 36 / 38 | 27 / 28 | 19 / 25 | 8 / 14 | 12 / 13 | 2 / 4 | 14 / 18 | 18 / 27 | 23 / 28 | 1 / 2 | 4 / 6 | 22 / 25 | 24 / 26 | 5 / 9 | 28 / 36 | 29 / 32 | 25 / 30 | 29 / 30 | 16 / 26 | 27 / 27 | 11 / 21 | 24 / 25 | 14 / 23 | 23 / 24 | 21 / 29 | 21 / 28 | 4 / 6 | 16 / 16 | 17 / 31 | 26 / 31 | 8 / 9 | 28 / 30 | 2 / 5 | 18 / 21 | 11 / 26 | 25 / 26 | 1 / 1 | 16 / 27 | 17 / 27 | 13 / 17 | 28 / 29 | 12 / 25 | 25 / 25 | 34 / 35 | 2 / 2 | 2 / 2 | 3 / 4 | 9 / 12 | 21 / 29 | 17 / 18 | 9 / 12 | 16 / 27 | 27 / 27 | 3 / 6 | 40 / 43 | 24 / 30 | 30 / 32 | 24 / 32 | 30 / 33 | 20 / 27 | 23 / 27 | 18 / 28 | 27 / 29 | 21 / 28 | 11 / 21 | 24 / 25 | 16 / 35 | 35 / 35 | 1 / 1 |
| serious Total, serious adverse events | 0 / 26 | 3 / 12 | 3 / 12 | 0 / 22 | 1 / 22 | 6 / 38 | 0 / 38 | 2 / 28 | 0 / 25 | 8 / 14 | 4 / 13 | 0 / 4 | 0 / 18 | 7 / 27 | 5 / 28 | 0 / 2 | 0 / 6 | 0 / 25 | 3 / 26 | 1 / 9 | 0 / 36 | 0 / 32 | 7 / 30 | 3 / 30 | 8 / 26 | 5 / 27 | 0 / 21 | 0 / 25 | 7 / 23 | 6 / 24 | 3 / 29 | 0 / 28 | 1 / 6 | 1 / 16 | 5 / 31 | 5 / 31 | 2 / 9 | 0 / 30 | 0 / 5 | 1 / 21 | 0 / 26 | 0 / 26 | 0 / 1 | 0 / 27 | 0 / 27 | 0 / 17 | 0 / 29 | 3 / 25 | 3 / 25 | 1 / 35 | 2 / 2 | 0 / 2 | 0 / 4 | 0 / 12 | 0 / 29 | 2 / 18 | 0 / 12 | 7 / 27 | 6 / 27 | 1 / 6 | 0 / 43 | 3 / 30 | 2 / 32 | 10 / 32 | 7 / 33 | 4 / 27 | 4 / 27 | 5 / 28 | 5 / 29 | 0 / 28 | 2 / 21 | 1 / 25 | 2 / 35 | 0 / 35 | 0 / 1 |
Outcome results
Primary
Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
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.
Population: HIV-infected women 2-12 weeks (14-84 days) post-delivery receiving ARV drug combinations AND starting postpartum contraceptives as listed in the protocol with intensive PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms | Before contraceptive initiation | 115.97 mcg*hr/mL |
| 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. | Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms | After contraceptive initiation | 100.20 mcg*hr/mL |
Comparison: The statistical analysis is for LPV PK.p-value: 0.11490% CI: [0.97, 1.59]Wilcoxon signed rank test
Primary
Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
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.
Population: HIV-infected women 2-12 weeks (14-84 days) post-delivery receiving one of the ARV drug combinations AND starting postpartum contraceptives as listed in the protocol with intensive PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms | Before contraceptive initiation | 53.96 mcg*hr/mL |
| 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. | Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms | After contraceptive initiation | 55.25 mcg*hr/mL |
| FPV/RTV 700/100mg b.i.d. | Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms | Before contraceptive initiation | 53.64 mcg*hr/mL |
| FPV/RTV 700/100mg b.i.d. | Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms | After contraceptive initiation | 56.65 mcg*hr/mL |
Comparison: The statistical test is for ATV PK.p-value: 0.36790% CI: [0.84, 1.44]Wilcoxon signed rank test
Comparison: The statistical test is for EFV PK.p-value: 0.56190% CI: [0.92, 1.13]Wilcoxon signed rank test
Primary
Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC (area under the curve) were determined using the linear trapezoidal rule. See PK target in the Protocol Appendix V.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or Postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 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. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 7 Participants |
| 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. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 16 Participants |
| 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. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 22 Participants |
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 23 Participants |
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 9 Participants |
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 20 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 13 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 24 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 23 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 22 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 15 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 23 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 24 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 10 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 18 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 8 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 18 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 10 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 4 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 3 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 14 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 5 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 1 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 2 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 12 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 34 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 33 Participants |
| TFV 300mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 22 Participants |
| TFV 300mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 26 Participants |
| TFV 300mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 8 Participants |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 1 Participants |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 12 Participants |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 12 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 27 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 27 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 2 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 12 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 11 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 1 Participants |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 20 Participants |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 21 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 27 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 30 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 9 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 11 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 30 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 33 Participants |
| ETR 200mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 13 Participants |
| ETR 200mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 5 Participants |
| ETR 200mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 7 Participants |
| MVC 150 or 300mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 7 Participants |
| MVC 150 or 300mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 8 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 9 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 19 Participants |
| DRV/RTV 800/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 22 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 7 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 22 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 19 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 29 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 8 Participants |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 27 Participants |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 7 Participants |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 23 Participants |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 32 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | NA Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 14 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 15 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 10 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 26 Participants |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 19 Participants |
| RPV 25mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 2nd Trimester | 14 Participants |
| RPV 25mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | Postpartum | 25 Participants |
| RPV 25mg q.d. | Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs | 3rd Trimester | 26 Participants |
Primary
Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose. See PK target in Protocol Appendix V. 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.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period. No data are available for LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug due to extremely low enrollment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 5 Participants |
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 7 Participants |
| FPV/RTV 700/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 16 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 6 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 6 Participants |
| DRV/RTV 600/100mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 4 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 1 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 4 Participants |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 4 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 3 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 2 Participants |
| EVG/COBI 150/150mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 0 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 13 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 11 Participants |
| DRV/COBI 800/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 9 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 8 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 8 Participants |
| ATV/COBI 300/150 mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 6 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 9 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 6 Participants |
| EFV 600 mg q.d. (Outside THA) | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 2 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 2nd Trimester | 4 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | 3rd Trimester | 8 Participants |
| ATV/RTV Arm 1: 300/100mg q.d. | Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs | Postpartum | 4 Participants |
Primary
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs
Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs | 2nd Trimester | NA ng*hour/mL |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs | 3rd Trimester | 2717 ng*hour/mL |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs | Postpartum | 3645 ng*hour/mL |
p-value: 0.00890% CI: [0.6, 0.88]t-test, 2 sided
Primary
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 55.1 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 79.6 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 51.8 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 43.50 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 51.60 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 32.15 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 45.9 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 45.8 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 61.7 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | NA mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 33.5 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 34.2 mg*hour/L |
p-value: 0.05590% CI: [0.44, 0.88]Wilcoxon signed-rank test
p-value: <0.00190% CI: [0.55, 0.73]Wilcoxon signed-rank test
p-value: 0.2290% CI: [0.44, 1.04]Wilcoxon signed-rank test
p-value: <0.00190% CI: [0.49, 0.72]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.64, 0.89]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.57, 0.88]Wilcoxon signed-rank test
p-value: 0.7890% CI: [0.71, 1.35]Wilcoxon signed-rank test
Primary
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 72 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | Postpartum | 133 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 96 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 6.6 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | Postpartum | 11.6 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 5.4 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 8.3 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 4.5 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | Postpartum | 5.3 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 14.9 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | Postpartum | 27.1 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 16.1 mg*hour/L |
p-value: <0.0590% CI: [0.42, 0.63]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.63, 0.84]Wilcoxon signed-rank test
p-value: 0.0390% CI: [0.34, 0.98]Wilcoxon signed-rank test
p-value: 0.00190% CI: [0.51, 0.89]Wilcoxon signed-rank test
p-value: 0.0684Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.49, 0.68]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.53, 0.68]Wilcoxon signed-rank test
Primary
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24 (area under the curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 47.6 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 65.0 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 49.2 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.271 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.171 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.212 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.216 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.197 mg*hour/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.206 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.257 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.181 mg*hour/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.283 mg*hour/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 21.0 mg*hour/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 15.3 mg*hour/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 14.0 mg*hour/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 50.00 mg*hour/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 42.05 mg*hour/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 95.55 mg*hour/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 36.20 mg*hour/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 25.33 mg*hour/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 18.85 mg*hour/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 60.02 mg*hour/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 47.30 mg*hour/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 62.70 mg*hour/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 41.9 mg*hour/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 57.9 mg*hour/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 88.2 mg*hour/L |
| TFV 300mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 2.4 mg*hour/L |
| TFV 300mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 1.9 mg*hour/L |
| TFV 300mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 3.0 mg*hour/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 28.8 mg*hour/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 39.6 mg*hour/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 14.5 mg*hour/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 63.5 mg*hour/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 64.6 mg*hour/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 103.9 mg*hour/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 30.6 mg*hour/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 48.8 mg*hour/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 45.7 mg*hour/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 58.7 mg*hour/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 37.7 mg*hour/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 26.2 mg*hour/L |
p-value: 0.00290% CI: [0.52, 0.75]Wilcoxon signed-rank test
p-value: 0.000390% CI: [0.63, 0.81]Wilcoxon signed-rank test
p-value: 0.0990% CI: [0.34, 0.98]Wilcoxon signed-rank test
p-value: 0.00490% CI: [0.54, 0.82]Wilcoxon signed-rank test
p-value: 0.2790% CI: [0.5, 1.27]Wilcoxon signed-rank test
p-value: 0.790% CI: [0.66, 1.12]Wilcoxon signed-rank test
p-value: 0.4690% CI: [0.29, 1.34]Wilcoxon signed-rank test
p-value: 0.590% CI: [0.63, 1.39]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.57, 1]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.42, 0.73]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.33, 0.68]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.36, 0.54]Wilcoxon signed-rank test
p-value: 0.187590% CI: [0.53, 1.04]Wilcoxon signed-rank test
p-value: 0.156390% CI: [0.19, 1.11]Wilcoxon signed-rank test
p-value: 0.24190% CI: [0.85, 1.03]Wilcoxon signed-rank test
p-value: 0.83790% CI: [0.9, 1.32]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.55, 0.88]Wilcoxon signed-rank test
p-value: 0.004690% CI: [0.72, 0.89]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.52, 0.85]Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
Primary
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the trapezoidal rule.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period. No 2nd trimester data were available for the EFV 600mg q.d. arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 55.4 mg*hour/L |
| 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. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | Postpartum | 58.3 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 1.669 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 1.969 mg*hour/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs | Postpartum | 2.387 mg*hour/L |
p-value: 0.0790% CI: [0.83, 1.13]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.61, 0.96]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.62, 1.03]Wilcoxon signed-rank test
Primary
PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 6.55 mg/L |
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 8.96 mg/L |
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 6.22 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.85 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 3.62 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 3.54 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 7.04 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 4.59 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 3.67 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 2.20 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.82 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 3.90 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 3.87 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.41 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.13 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 5.61 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 6.75 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.12 mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | NA mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 3.6 mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.1 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.298 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.245 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.250 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 2.5 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 1.2 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.1 mg/L |
| TFV 300mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.44 mg/L |
| TFV 300mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 5.10 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 8.11 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 6.77 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.78 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.53 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 5.64 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 7.78 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 4.51 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 3.11 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.52 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.73 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 3.56 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 5.43 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 5.0 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | NA mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 5.1 mg/L |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 3.89 mg/L |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 3.62 mg/L |
| IDV/RTV Arm 2: 400/100mg q.d. (Only THA) | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs | Postpartum | 5.37 mg/L |
p-value: 0.00790% CI: [1.01, 1.56]Wilcoxon signed rank test
Comparison: FPV was analyzed as the form of amprenavir (APV). FPV is the prodrug of APV.p-value: 0.1690% CI: [0.56, 1.22]Wilcoxon signed rank test
p-value: 0.14890% CI: [0.64, 1.01]Wilcoxon signed-rank test
p-value: <0.00190% CI: [0.62, 0.81]Wilcoxon signed-rank test
p-value: 0.009890% CI: [0.61, 0.89]Wilcoxon signed-rank test
p-value: 0.002590% CI: [0.64, 0.88]Wilcoxon signed rank test
p-value: <0.000190% CI: [0.46, 0.64]Wilcoxon signed rank test
p-value: 0.002490% CI: [0.41, 0.76]Wilcoxon signed rank test
p-value: 0.43890% CI: [0.499, 1.269]Wilcoxon signed rank test
p-value: 0.21990% CI: [0.186, 1.512]Wilcoxon signed rank test
p-value: 0.29690% CI: [0.94, 1.18]Wilcoxon signed rank test
Comparison: FPV was analyzed in the form of amprenavir (APV). FPV is the prodrug of APV.p-value: 0.0390% CI: [0.58, 0.93]Wilcoxson signed rank test
Comparison: This analysis was for ATV.p-value: >0.0590% CI: [0.68, 1.08]Wilcoxon signed rank test
p-value: 0.163690% CI: [0.79, 1.01]Wilcoxon signed rank test
Comparison: This analysis was for ATV.p-value: <0.0590% CI: [0.53, 0.91]Wilcoxon signed rank test
p-value: 0.1690% CI: [0.99, 1.24]Wilcoxon signed rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: 0.6790% CI: [0.85, 1.34]Wilcoxon signed-rank test
p-value: 0.0890% CI: [0.59, 0.91]Wilcoxon signed rank test
p-value: <0.0190% CI: [0.55, 0.72]Wilcoxon signed rank test
Primary
PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 8.4 mg/L |
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | Postpartum | 14.6 mg/L |
| 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. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 10.7 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 2.250 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | Postpartum | 3.035 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 1.770 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 1.01 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.70 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | Postpartum | 0.63 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.145 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | Postpartum | 0.134 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 0.134 mg/L |
p-value: <0.0590% CI: [0.48, 0.68]Wilcoxon signed rank test
p-value: <0.0590% CI: [0.62, 0.85]Wilcoxon signed rank test
p-value: 0.09Wilcoxon signed rank test
p-value: 0.003Wilcoxon signed rank test
p-value: 0.036Wilcoxon signed rank test
p-value: >0.0590% CI: [0.69, 1.02]Wilcoxon signed rank test
p-value: >0.0590% CI: [0.68, 1.01]Wilcoxon signed rank test
Primary
PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs | 3rd Trimester | 448 ng/mL |
| 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. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs | Postpartum | 647 ng/mL |
| Unknown | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs | 2nd Trimester | — ng/mL |
p-value: 0.00790% CI: [0.58, 0.85]Wilcoxon signed rank test
Primary
PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 69.7 ng/mL |
| 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. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | Postpartum | 133 ng/mL |
| 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. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 96 ng/mL |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 80.4 ng/mL |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | Postpartum | 98.2 ng/mL |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 91.2 ng/mL |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 107 ng/mL |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 87.8 ng/mL |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | Postpartum | 141 ng/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 1447.1 ng/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | Postpartum | 1713.1 ng/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 1432.8 ng/mL |
p-value: 0.1490% CI: [0.34, 1.09]Wilcoxon signed rank test
p-value: 0.00290% CI: [0.5, 0.81]Wilcoxon signed rank test
p-value: 0.2490% CI: [0.49, 1.23]Wilcoxon signed rank test
p-value: 0.5390% CI: [0.6, 1.17]Wilcoxon signed rank test
p-value: 0.290% CI: [0.3, 1.11]Wilcoxon signed rank test
p-value: 0.1290% CI: [0.58, 1.55]Wilcoxon signed rank test
p-value: 0.35890% CI: [0.71, 1.2]Wilcoxon signed rank test
p-value: 0.015690% CI: [0.55, 0.93]Wilcoxon signed rank test
Primary
PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period. No 2nd trimester data were available for the MVC 150 or 300mg b.i.d. arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 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. | PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs | 3rd Trimester | 108 ng/mL |
| 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. | PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs | Postpartum | 128 ng/mL |
| Unknown | PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs | 2nd Trimester | — ng/mL |
p-value: 0.190% CI: [0.72, 1.01]t-test, 2 sided
Primary
PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.84 mg/L |
| 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. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 4.51 mg/L |
| 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. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 2.52 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.12 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 2.87 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 1.64 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 2.22 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.12 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 2.51 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | NA mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.52 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.47 mg/L |
p-value: 0.10990% CI: [0.39, 1.12]Wilcoxon signed-rank test
p-value: <0.00190% CI: [0.49, 0.69]Wilcoxon signed-rank test
p-value: 0.4490% CI: [0.14, 1.65]Wilcoxon signed-rank test
p-value: <0.00190% CI: [0.43, 0.72]Wilcoxon signed-rank test
p-value: 0.4390% CI: [0.63, 1.1]Wilcoxon signed-rank test
p-value: 0.3190% CI: [0.69, 1.44]Wilcoxon signed-rank test
p-value: 0.4990% CI: [0.71, 1.16]Wilcoxon signed-rank test
Primary
PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 3.7 mg/L |
| 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. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | Postpartum | 7.2 mg/L |
| 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. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 5.1 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.0621 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | Postpartum | 0.0797 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 0.064 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 0.48 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.36 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | Postpartum | 0.38 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.13 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | Postpartum | 0.28 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 0.13 mg/L |
p-value: <0.0590% CI: [0.32, 0.63]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.58, 0.88]Wilcoxon signed-rank test
p-value: 0.0290% CI: [0.23, 0.78]Wilcoxon signed-rank test
p-value: 0.390% CI: [0.56, 1.08]Wilcoxon signed-rank test
p-value: 0.036Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.32, 0.52]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.41, 0.57]Wilcoxon signed-rank test
Primary
PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose. For the TAF 25 mg q.d., 10 mg q.d. w/COBI, and 25 mg q.d. w/COBI or RTV boosting arms, samples were all below the limit of quantification and statistical analyses were not conducted.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.73 mg/L |
| 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. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 1.28 mg/L |
| 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. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.93 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.00195 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.00195 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.00195 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.00195 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.00195 mg/L |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.00195 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.00195 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.00195 mg/L |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.00195 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.3771 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.0258 mg/L |
| EVG/COBI 150/150mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.0487 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.33 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.27 mg/L |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 1.43 mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.61 mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.21 mg/L |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.21 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 1.48 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 1.49 mg/L |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 1.94 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.7 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 1.2 mg/L |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 2.0 mg/L |
| TFV 300mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.054 mg/L |
| TFV 300mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.039 mg/L |
| TFV 300mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.061 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.5 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.8 mg/L |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.3 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 1.17 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.99 mg/L |
| DRV/RTV 800/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 2.78 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.49 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 0.90 mg/L |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.71 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | Postpartum | 1.26 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 3rd Trimester | 0.57 mg/L |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs | 2nd Trimester | 0.44 mg/L |
p-value: 0.003990% CI: [0.35, 0.68]Wilcoxon signed-rank test
p-value: 0.006290% CI: [0.52, 0.84]Wilcoxon signed-rank test
p-value: <0.1Wilcoxon signed-rank test
p-value: <0.1Wilcoxon signed-rank test
p-value: <0.190% CI: [0.08, 0.3]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.12, 0.36]Wilcoxon signed-rank test
p-value: <0.190% CI: [0.2, 0.51]Wilcoxon signed-rank test
p-value: >0.190% CI: [0.11, 0.94]Wilcoxon signed-rank test
p-value: 0.07990% CI: [0.78, 0.97]Wilcoxon signed-rank test
p-value: 0.0190% CI: [0.77, 1.09]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.37, 0.72]Wilcoxon signed-rank test
p-value: 0.032590% CI: [0.71, 0.96]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.54, 0.77]Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: >0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
p-value: <0.05Wilcoxon signed-rank test
Primary
PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.
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.
Population: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time period. No 2nd trimester data were available for the EFV 600mg q.d. arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 1.60 mg/L |
| 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. | PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | Postpartum | 2.05 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | 2nd Trimester | 0.063 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | 3rd Trimester | 0.056 mg/L |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs | Postpartum | 0.081 mg/L |
p-value: <0.0590% CI: [0.73, 1.06]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.55, 0.9]Wilcoxon signed-rank test
p-value: <0.0590% CI: [0.57, 1.23]Wilcoxon signed-rank test
Primary
Plasma Concentration for Contraceptives
Serum concentrations of the contraceptives. Note that no historical controls were provided by team pharmacologists and thus no comparisons were done for contraceptive concentrations in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.
Time frame: Measured at 6-7 weeks after contraceptive initiation postpartum
Population: HIV-infected women 2-12 weeks (14-84 days) post-delivery receiving ARV drug combinations AND starting postpartum contraceptives as listed in the protocol with intensive PK results.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 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. | Plasma Concentration for Contraceptives | 604 pg/mL |
| FPV/RTV 700/100mg b.i.d. | Plasma Concentration for Contraceptives | 428 pg/mL |
| DRV/RTV 600/100mg b.i.d. | Plasma Concentration for Contraceptives | 125 pg/mL |
Secondary
Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs
Infant plasma concentrations were collected and measured during the first 9 days of life.
Time frame: Blood samples were collected at 2-10, 18-28, 36-72 hours and 5-9 days after birth.
Population: All infants who met the requirements for washout PK sampling (as specified in Protocol Section 4.4) with plasma samples drawn after delivery. Infants don't need to contribute to all time points to be included. For DRV/COBI 800/150mg q.d. arm, infants with concentrations below detection limit were not summarized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 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. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 2-10 hours after birth | 1.73 mcg/mL |
| 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. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 18-28 hours after birth | 1.53 mcg/mL |
| 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. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 36-72 hours after birth | 1.00 mcg/mL |
| 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. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 5-9 days after birth | 0.06 mcg/mL |
| FPV/RTV 700/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 18-28 hours after birth | 0.032 mcg/mL |
| FPV/RTV 700/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 36-72 hours after birth | 0.005 mcg/mL |
| FPV/RTV 700/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 5-9 days after birth | 0.005 mcg/mL |
| FPV/RTV 700/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 2-10 hours after birth | 0.132 mcg/mL |
| DRV/RTV 600/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 36-72 hours after birth | 1.87 mcg/mL |
| DRV/RTV 600/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 18-28 hours after birth | 1.43 mcg/mL |
| DRV/RTV 600/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 5-9 days after birth | 1.72 mcg/mL |
| DRV/RTV 600/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 2-10 hours after birth | 0.35 mcg/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 5-9 days after birth | 0.4 mcg/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 18-28 hours after birth | 1.0 mcg/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 2-10 hours after birth | 1.1 mcg/mL |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Concentration of ARVs and TB Drugs | 36-72 hours after birth | 0.9 mcg/mL |
Secondary
Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs
Infant plasma concentrations were collected and measured during the first 9 days of life. Half-life is defined as 0.693/k, where k, the elimination rate constant, is the slope of the decline in concentrations.
Time frame: Infant plasma samples at 2-10, 18-28, 36-72 hours and 5-9 days after birth.
Population: All infants who met the requirement for washout PK sampling (as specified in Protocol Section 4.4) with plasma samples drawn after delivery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 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. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs | 32.8 hour |
| FPV/RTV 700/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs | 7.6 hour |
| DRV/RTV 600/100mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs | NA hour |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | Pharmacokinetic (PK) Parameter: Infant Plasma Washout Half-life (T1/2) of ARVs and TB Drugs | 65.6 hour |
Secondary
PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs
Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio.
Time frame: Measured at time of delivery with single cord blood and single maternal plasma sample.
Population: All participants with cord blood drawn immediately after the cord was clamped and maternal blood samples drawn at the time the cord was clamped at delivery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 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. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 0.15 unitless |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 1.25 unitless |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 0.91 unitless |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 0.07 unitless |
| EVG/COBI 150/150mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 0.07 unitless |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (IQR) for ARVs and TB Drugs | 0.88 unitless |
Secondary
PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs
Cord blood and maternal plasma concentrations were collected and measured at delivery, and compared as a ratio. For arms with zero overall participants analyzed, samples were below the limit of quantification and ratios could not be calculated.
Time frame: Measured at time of delivery with single cord blood and single maternal plasma sample.
Population: All participants with cord blood drawn immediately after the cord was clamped and maternal blood samples drawn at the time the cord was clamped at delivery.~Notes: a) Ratios were not calculated for the TAF 25mg q.d. and TAF 25mg q.d. w/COBI or RTV Boosting arms since all cord blood samples were below the lower limit of quantification. b)These arms were combined for analysis: (1) ATV/RTV 300/100mg q.d. \& TFV/ATV/RTV 300/300/100mg q.d. and (2) DRV/RTV 800/100mg q.d. \& DRV/RTV 600/100mg b.i.d.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 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. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.97 unitless |
| FPV/RTV 700/100mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.67 unitless |
| DRV/RTV 600/100mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.49 unitless |
| NFV Arm 2: 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.2 unitless |
| EVG/COBI 150/150mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 1.5 unitless |
| DRV/COBI 800/150 mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.52 unitless |
| ATV/COBI 300/150 mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.33 unitless |
| EFV 600 mg q.d. (Outside THA) | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.14 unitless |
| ATV/RTV Arm 1: 300/100mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.16 unitless |
| TFV 300mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.19 unitless |
| TFV/ATV/RTV Arm 1: 300/300/100mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.12 unitless |
| DRV/RTV 800/100mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.55 unitless |
| ATV/RTV Arm 2: 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.18 unitless |
| TFV/ATV/RTV Arm 2: 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. | PK Parameter: Cord/Maternal Blood Concentration Ratio With Median (Range) for ARVs and TB Drugs | 0.18 unitless |
Other Pre-specified
Adverse Events of Grade 3 or Higher
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured through 24 weeks postpartum
Other Pre-specified
Adverse Pregnancy Outcome: Congenital Anomalies
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which werenot conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured through 24 weeks of life
Other Pre-specified
Adverse Pregnancy Outcome: Fetal Demise
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured through 24 weeks postpartum
Other Pre-specified
Adverse Pregnancy Outcome: Low Birth Weight
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured at delivery
Other Pre-specified
Adverse Pregnancy Outcome: Preterm Birth
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured through delivery
Other Pre-specified
ARV Concentrations in Plasma
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belong with Other outcome measures (see SAP).
Time frame: Measured at intensive PK visit
Other Pre-specified
ARV Concentrations in Vaginal Secretions
The original study protocol listed this PK parameter under secondary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
Time frame: Measured at intensive PK visit
Other Pre-specified
ARV Exposure (as Measured by Area Under the Curve or Other PK Parameters) During Pregnancy and Postpartum According to Genotype
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured at intensive PK visit
Other Pre-specified
Drug Parameter: Clearance Over Systemic Availability (Cl/F)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Drug Parameter: Half-life (t1/2)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Drug Parameter: Minimum Concentration (Cmin)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Drug Parameter: Pre-dose Concentration (Cdose)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Drug Parameter: Time After Administration of Drug When Maximum Plasma Concentration is Reached (Tmax)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Drug Parameter: Volume of Distribution Over Systemic Availability (V/F)
The original study protocol listed this PK parameter under primary outcome measures. However, this PK parameter was intended for potential supporting analyses and thus belongs with Other outcome measures (see SAP).
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.
Other Pre-specified
Infant HIV Infection Status
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured through 24 weeks of life
Other Pre-specified
Infant Neurological Events of Grade 1 or Higher
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP). See Adverse events section for adverse events.
Time frame: Measured through 24 weeks of life
Other Pre-specified
Rate of Detection of HIV RNA/DNA in Vaginal Secretions and Comparison to Level in Blood
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured at intensive PK visit
Other Pre-specified
Rate of Detection of Study Drugs in Vaginal Secretions
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured at intensive PK visit
Other Pre-specified
Ratio of Unbound/Total Drug Concentrations
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured at time of delivery
Other Pre-specified
Ratio of Vaginal Drug Concentrations to Simultaneous Blood Concentrations
The original study protocol listed all non-primary outcome measures under secondary outcome measures without distinguishing between secondary vs other outcome measures. This outcome measure was intended for potential supporting analyses which were not conducted (see SAP).
Time frame: Measured at intensive PK visit