Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,578
- 试验地点
- 62
- 主要终点
- PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must belong to one of the following 5 groups:
- •HIV-infected pregnant women greater than or equal to 20 weeks gestation NOT on TB treatment receiving one or more of the ARV drugs/drug combinations specified in the protocol
- •HIV-infected pregnant women greater than or equal to 20 weeks gestation receiving one of the ARV drugs/drug combinations specified in the protocol and TB treatment with at least one of the TB drugs, specified in the protocol, at study entry
- •HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the first-line TB drugs, specified in the protocol, at study entry
- •HIV-infected and HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the second-line TB drugs, specified in the protocol, at study entry
- •HIV-infected women 2 to 12 weeks (14 to 84 days) post-delivery receiving one of the ARV drug combinations listed in the protocol AND starting postpartum contraceptives as listed in the protocol
- •The woman must be stable on the ARV drug/drug combination and/or TB drug combination for at least 2 weeks prior to PK sampling
- •If a woman is receiving a specific generic ARV formulation, the protocol team has approved this formulation
- •HIV-infected pregnant women must be planning to continue on current ARV regimen until postpartum PK sampling is completed. HIV-infected postpartum women on hormonal contraceptives must be planning to continue on ARV and contraceptive regimens until final PK sampling is completed
- •For HIV-infected women: confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry. More information on this criterion can be found in the protocol.
- •HIV-uninfected pregnant women must have documented negative HIV antibody test during current pregnancy. Note: adequate source documentation, including the date of specimen collection, date of testing, test performed, and test result, must be available.
- •Participants enrolling in the 3rd trimester must enroll by 37 6/7 weeks gestation
- •Participant can provide legal informed consent per local regulations
- •If a woman has completed this study and becomes pregnant again, she may re-enroll in the study only if she is enrolled in a different arm than that studied during her initial enrollment
排除标准
- •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)
研究组 & 干预措施
EFV 600 mg q.d. (outside THA)
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received efavirenz (EFV) 600 mg q.d. (Participants outside of Thailand only)
干预措施: efavirenz (Drug)
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received:
darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
干预措施: darunavir/ritonavir dosage #1 (Drug)
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received:
darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
干预措施: darunavir/ritonavir dosage #2 (Drug)
TAF 25mg q.d. w/COBI or RTV boosting
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received tenofovir alafenamide fumarate (TAF) 25 mg q.d. with cobicistat (COBI) or ritonavir (RTV) boosting.
干预措施: TAF w/cobicistat or ritonavir (Drug)
DRV/RTV 600 or 800 or 900/100mg b.i.d. then 800 or 900/100mg b.i.d. then 600/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received:
darunavir/ritonavir (DRV/RTV) 600/100 mg twice daily (b.i.d.) or 800/100 mg b.i.d. until 30 weeks gestation; then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
OR darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after postpartum hospital discharge until 2 week postpartum PK samples are drawn.
干预措施: darunavir/ritonavir dosage #3 (Drug)
DTG 50mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received dolutegravir (DTG) 50 mg once a day (q.d.).
干预措施: dolutegravir (Drug)
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.
干预措施: tenofovir alafenamide fumarate (TAF) (Drug)
TAF 10mg q.d. w/COBI
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received tenofovir alafenamide fumarate (TAF) 10 mg q.d. with cobicistat (COBI).
干预措施: TAF w/cobicistat (Drug)
EVG/COBI 150/150mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received elvitegravir/cobicistat (EVG/COBI) 150/150 mg q.d
干预措施: elvitegravir/cobicistat (Drug)
DRV/COBI 800/150 mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d.
干预措施: darunavir/cobicistat (Drug)
ATV/COBI 300/150 mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment who received atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d.
干预措施: atazanavir/cobicistat (Drug)
EFV 600mg q.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: efavirenz (Drug)
EFV 600mg q.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: rifampicin (Drug)
EFV 600mg q.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: ethambutol (Drug)
EFV 600mg q.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: isoniazid (Drug)
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: lopinavir/ritonavir dosage #1 (Drug)
EFV 600mg q.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600mg q.d.and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: pyrazinamide (Drug)
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: rifampicin (Drug)
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: ethambutol (Drug)
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: isoniazid (Drug)
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.
干预措施: ethambutol (Drug)
LPV/RTV 800/200mg b.i.d. and at least one 1st line TB drug
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 800/200mg b.i.d. and TB treatment with at least one of the following TB drugs at study entry:
- rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: pyrazinamide (Drug)
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.
干预措施: rifampicin (Drug)
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.
干预措施: isoniazid (Drug)
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.
干预措施: pyrazinamide (Drug)
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
干预措施: kanamycin (Drug)
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
干预措施: amikacin (Drug)
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
干预措施: capreomycin (Drug)
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
干预措施: moxifloxacin (Drug)
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
干预措施: levoflaxacin (Drug)
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
干预措施: ofloxacin (Drug)
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
干预措施: ethionamide/prothionamide (Drug)
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
干预措施: terizidone/cycloserine (Drug)
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
干预措施: para-aminosalicylic acid (PAS) (Drug)
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
干预措施: high dose INH (Drug)
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
干预措施: bedaquiline (Drug)
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
干预措施: clofazamine (Drug)
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
干预措施: delamanid (Drug)
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
干预措施: linezolid (Drug)
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
干预措施: pretomanid (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
干预措施: atazanavir/cobicistat (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
干预措施: darunavir/cobicistat (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol
干预措施: ethinyl estradiol (Drug)
FPV/RTV 700/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received fosamprenavir/ritonavir (FPV/RTV)700/100mg twice a day
干预措施: fosamprenavir/ritonavir (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
干预措施: atazanavir/cobicistat (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
干预措施: darunavir/cobicistat (Drug)
DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d with ENG
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received darunavir/cobicistat (DRV/COBI) 800/150 mg q.d. or atazanavir/cobicistat (ATV/COBI) 300/150 mg q.d. postpartum and starting etonogestrel (ENG) implant
干预措施: etonogestrel implant (Drug)
EFV 600mg q.d. with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received efavirenz (EFV) 600mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: efavirenz (Drug)
EFV 600mg q.d. with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received efavirenz (EFV) 600mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: ethinyl estradiol (Drug)
ATV/RTV/TFV 300/100/300mg q.d. with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: atazanavir/ritonavir/tenofovir dosage #1 (Drug)
ATV/RTV/TFV 300/100/300mg q.d. with 30-35ug EE
HIV-infected women 2-12 weeks (14-84 days) post-delivery who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: ethinyl estradiol (Drug)
NVP 200mg b.i.d
HIV-infected pregnant women ≥ 26 weeks gestation who received nevirapine (NVP) 200 mg twice a day
干预措施: nevirapine (Drug)
APV 1200mg b.i.d
HIV-infected pregnant women ≥ 26 weeks gestation who received amprenavir (APV) 1200mg twice a day
干预措施: amprenavir (Drug)
ABC 300mg b.i.d
HIV-infected pregnant women ≥ 20 weeks gestation who received abacavir (ABC) 300mg twice a day
干预措施: abacavir (Drug)
LPV/RTV Arm 1: 400/100mg b.i.d
HIV-infected pregnant women ≥ 26 weeks gestation who received lopinavir/ritonavir (LPV/RTV) 400/100mg twice a day
干预措施: lopinavir/ritonavir dosage #2 (Drug)
IDV/RTV Arm 1: 800/100mg b.i.d
HIV-infected pregnant women ≥ 26 weeks gestation who received indinavir/ritonavir (IDV/RTV) 800/100 mg twice a day
干预措施: indinavir/ritonavir dosage #1 (Drug)
LPV/RTV Arm 2: 400/100mg b.i.d. then 533/133mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received Kaletra (LPV/RTV) 400/100 mg twice a day until 30 weeks gestation, then 533/133 mg twice a day until results of postpartum PK evaluation were available
干预措施: lopinavir/ritonavir dosage #2 (Drug)
LPV/RTV Arm 2: 400/100mg b.i.d. then 533/133mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received Kaletra (LPV/RTV) 400/100 mg twice a day until 30 weeks gestation, then 533/133 mg twice a day until results of postpartum PK evaluation were available
干预措施: lopinavir/ritonavir dosage #3 (Drug)
ATV/RTV Arm 1: 300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day
干预措施: atazanavir/ritonavir dosage #1 (Drug)
DDI 400mg or 250mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received didanosine delayed release (Videx® EC) (DDI) 400 mg once a day if weight > 60 kg; 250 mg once a day if weight < 60 kg
干预措施: didanosine delayed release (Videx® EC) (Drug)
FTC 200mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received emtricitabine (FTC) 200 mg once a day
干预措施: emtricitabine (Drug)
TFV 300mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir (TFV) 300 mg once a day
干预措施: tenofovir (Drug)
TFV/ATV/RTV Arm 1: 300/300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day
干预措施: atazanavir/ritonavir/tenofovir dosage #1 (Drug)
NFV Arm 1: 1250mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) [625 mg tablets] 1250 mg twice a day
干预措施: nelfinavir dosage #1 (Drug)
EFV 600mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received efavirenz (EFV) 600 mg once a day
干预措施: efavirenz (Drug)
TPV/RTV 500/200mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received tipranavir/ritonavir (TPV/RTV) 500/200 mg twice a day
干预措施: tipranavir/ritonavir (Drug)
LPV/RTV Arm 3: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) tablets 400/100 mg [2 tablets] twice a day until 30 weeks gestation, then 600/150 mg [3 tablets] twice a day until postpartum hospital discharge; and 400/100 mg [2 tablets] twice a day after postpartum hospital discharge, until 2 week postpartum PK sample is drawn
干预措施: lopinavir/ritonavir dosage #2 (Drug)
LPV/RTV Arm 3: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV) tablets 400/100 mg [2 tablets] twice a day until 30 weeks gestation, then 600/150 mg [3 tablets] twice a day until postpartum hospital discharge; and 400/100 mg [2 tablets] twice a day after postpartum hospital discharge, until 2 week postpartum PK sample is drawn
干预措施: lopinavir/ritonavir dosage #4 (Drug)
RPV 25mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received rilpivirine (RPV) (25 mg q.d.)
干预措施: rilpivirine (Drug)
RAL 400mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received raltegravir (RAL) 400 mg twice a day
干预措施: raltegravir (Drug)
ETR 200mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received etravirine (ETR) 200mg twice a day
干预措施: etravirine (Drug)
MVC 150 or 300mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received maraviroc (MVC)150 mg or 300 mg twice a day
干预措施: maraviroc (Drug)
DRV/RTV 800/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir (DRV/RTV) 800/100 mg once a day
干预措施: darunavir/ritonavir dosage #4 (Drug)
DRV/RTV 600/100mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received darunavir/ritonavir (DRV/RTV) 600/100 mg twice a day
干预措施: darunavir/ritonavir dosage #1 (Drug)
ATV/RTV Arm 2: 300/100mg q.d. then 400/100mg q.d. then 300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day until 30 weeks gestation then 400/100 mg once a day until postpartum hospital discharge; then 300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: atazanavir/ritonavir dosage #1 (Drug)
ATV/RTV Arm 2: 300/100mg q.d. then 400/100mg q.d. then 300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received atazanavir/ritonavir (ATV/RTV) 300/100 mg once a day until 30 weeks gestation then 400/100 mg once a day until postpartum hospital discharge; then 300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: atazanavir/ritonavir dosage #2 (Drug)
TFV/ATV/RTV Arm 2: 300/300/100mg q.d. then 300/400/100mg q.d then 300/300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day until 30 weeks gestation; then 300/400/100 mg once a day until postpartum hospital discharge; then 300/300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: atazanavir/ritonavir/tenofovir dosage #1 (Drug)
TFV/ATV/RTV Arm 2: 300/300/100mg q.d. then 300/400/100mg q.d then 300/300/100mg q.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received tenofovir/atazanavir/ritonavir (TFV/ATV/RTV) 300/300/100 mg once a day until 30 weeks gestation; then 300/400/100 mg once a day until postpartum hospital discharge; then 300/300/100 mg once a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: tenofovir/atazanavir/ritonavir dosage #2 (Drug)
NFV Arm 2: 1250mg b.i.d. then 1875mg b.i.d. then 1250mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) [625 mg tablets] 1250 mg twice a day until 30 weeks gestation; then 1875 mg twice a day until postpartum hospital discharge; then 1250 mg twice a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: nelfinavir dosage #1 (Drug)
NFV Arm 2: 1250mg b.i.d. then 1875mg b.i.d. then 1250mg b.i.d.
HIV-infected pregnant women ≥ 20 weeks gestation who received nelfinavir (NFV) [625 mg tablets] 1250 mg twice a day until 30 weeks gestation; then 1875 mg twice a day until postpartum hospital discharge; then 1250 mg twice a day after postpartum hospital discharge until 2 week postpartum PK samples drawn
干预措施: nelfinavir dosage #2 (Drug)
IDV/RTV Arm 2: 400/100mg q.d. (only THA)
HIV-infected pregnant women ≥ 20 weeks gestation who received indinavir/ritonavir (IDV/RTV) 400/100 mg twice a day only to participants enrolling in Thailand
干预措施: indinavir/ritonavir dosage #2 (Drug)
LPV/RTV Arm 4: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d. (only African sites)
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV, Alluvia tablets) 400/100 mg [2 tablets] twice day until 30 weeks gestation; then 600/150 mg [3 tablets] twice a day until postpartum hospital discharge; then 400/100 mg [2 tablets] twice a day after postpartum hospital discharge until 2 week postpartum PK sample drawn only to participants enrolling in Uganda
干预措施: lopinavir/ritonavir dosage #2 (Drug)
LPV/RTV Arm 4: 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d. (only African sites)
HIV-infected pregnant women ≥ 20 weeks gestation who received lopinavir/ritonavir (LPV/RTV, Alluvia tablets) 400/100 mg [2 tablets] twice day until 30 weeks gestation; then 600/150 mg [3 tablets] twice a day until postpartum hospital discharge; then 400/100 mg [2 tablets] twice a day after postpartum hospital discharge until 2 week postpartum PK sample drawn only to participants enrolling in Uganda
干预措施: lopinavir/ritonavir dosage #4 (Drug)
EFV 600mg q.d. with ENG
HIV-infected women 2-12 weeks postpartum who received efavirenz (EFV) 600mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: etonogestrel implant (Drug)
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug
HIV-infected pregnant women > 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry:
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: ethambutol (Drug)
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug
HIV-infected pregnant women > 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry:
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: isoniazid (Drug)
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug
HIV-infected pregnant women > 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry:
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: pyrazinamide (Drug)
NVP 200mg b.i.d. and RIF and at least one 1st line TB drug
HIV-infected pregnant women > 20 weeks gestation who received nevirapine (NVP) 200 mg b.i.d AND rifampicin 8-12 mg/kg (max 600 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w. and at least one of the following drugs at study entry:
- ethambutol 15-20 mg/kg q.d., 25-35 mg/kg t.i.w.
- isoniazid 4-6 mg/kg (max 300 mg) q.d.; 8-12 mg/kg (max 900 mg) t.i.w.
- pyrazinamide 20-30mg/kg q.d.; 30-40mg/kg t.i.w.
干预措施: nevirapine (Drug)
ATV/RTV/TFV 300/100/300mg q.d. with ENG
HIV- infected women 2-12 weeks postpartum who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: atazanavir/ritonavir/tenofovir dosage #1 (Drug)
ATV/RTV/TFV 300/100/300mg q.d. with ENG
HIV- infected women 2-12 weeks postpartum who received atazanavir/ritonavir/tenofovir (ATV/RTV/TFV) 300/100/300 mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: etonogestrel implant (Drug)
LPV/RTV 400/100 b.i.d. with 30-35ug EE
HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: ethinyl estradiol (Drug)
LPV/RTV 400/100 b.i.d. with 30-35ug EE
HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting combined oral contraceptives formulated with 30-35 μg ethinyl estradiol (EE)
干预措施: lopinavir/ritonavir dosage #2 (Drug)
LPV/RTV 400/100 b.i.d. with ENG
HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: etonogestrel implant (Drug)
LPV/RTV 400/100 b.i.d. with ENG
HIV- infected women 2-12 weeks postpartum who received lopinavir/ritonavir (LPV/RTV) 400/100 b.i.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: lopinavir/ritonavir dosage #2 (Drug)
EFV 600mg q.d. with ENG
HIV-infected women 2-12 weeks postpartum who received efavirenz (EFV) 600mg q.d. postpartum and starting postpartum etonogestrel (ENG) implant
干预措施: efavirenz (Drug)
结局指标
主要结局
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs
时间窗: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (Range) for ARVs and TB Drugs
时间窗: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12 (area under the curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Geometric Mean (95% CI) for ARVs and TB Drugs
时间窗: Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing.
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (IQR) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24 (area under the curve from 0 to 24 hours) were determined using the linear trapezoidal rule.
PK Parameter: Area Under the Curve From 0 to 24 Hours (AUC24) With Median (Range) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC24h (area-under-the-curve from 0 to 24 hours) were determined using the trapezoidal rule.
PK Parameter: Maximum Concentration (Cmax) in mg/L With Median (IQR) for ARVs and TB Drugs
时间窗: 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
时间窗: 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
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Maximum Concentration (Cmax) in ng/mL With Median (95% CI) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm; Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8,12 (and 24) hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Cmax was the maximum observed concentration after a dose.
PK Parameter: Trough Concentration (C12) With Median (IQR) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C12) With Median (Range) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation); 3rd trimester (30-38 gestation); and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum, depending on study arm. Trough concentration was measured 12 hrs after an observed dose.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C12) With Geometric Mean (95% CI) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 12 hrs after an observed dose.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 12h post-dose sample after an observed dose.
PK Parameter: Trough Concentration (C24) With Median (IQR) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose. For the TAF 25 mg q.d., 10 mg q.d. w/COBI, and 25 mg q.d. w/COBI or RTV boosting arms, samples were all below the limit of quantification and statistical analyses were not conducted.
PK Parameter: Trough Concentration (C24) With Median (Range) for ARVs and TB Drugs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Trough concentration was measured 24 hrs after an observed dose.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. Trough concentration was the measured concentration from the 24h post-dose sample after an observed dose.
Number of Women Who Met PK Target of Area Under the Curve (AUC) for ARVs
时间窗: Measured at 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, 12 (and 24) hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC (area under the curve) were determined using the linear trapezoidal rule. See PK target in the Protocol Appendix V.
Number of Women Who Met PK Target of Maximum Concentration (Cmax) for First Line TB Drugs
时间窗: 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.
Plasma Concentration for Contraceptives
时间窗: Measured at 6-7 weeks after contraceptive initiation postpartum
Serum concentrations of the contraceptives. Note that no historical controls were provided by team pharmacologists and thus no comparisons were done for contraceptive concentrations in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.
Area Under the Curve From 0 to 12 Hours (AUC12) of ARVs for Contraceptive Arms
时间窗: Measured at 2-12 wks postpartum before contraceptive initiation and 6-7 wks after contraceptive initiation. Blood samples were drawn pre-dose and at 0, 1, 2, 6, 8 and 12 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods. AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear trapezoidal rule.
Area Under the Curve From 0 to 24 Hours (AUC24) of ARVs for Contraceptive Arms
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)
- 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.)