Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries (PROMISE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01061151
First received: February 1, 2010
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to examine effective methods of preventing the transmission of HIV from mother to child during pregnancy, labor and delivery, and breastfeeding. This is one part of the three-part PROMISE study and will be conducted at locations in Africa and other parts of the world where women typically receive a short course of highly active antiretroviral therapy (HAART) during pregnancy and where breastfeeding is common.


Condition Intervention
HIV Infections
Drug: Zidovudine (ZDV)
Drug: Nevirapine (NVP)
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])
Drug: Lamivudine-Zidovudine (3TC-ZDV)
Drug: Lopinavir-ritonavir (LPV-RTV)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Breastfeeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Antepartum Component: Confirmed presence of infant HIV infection [ Time Frame: Measured at birth or Week 1 study visit ] [ Designated as safety issue: Yes ]
    Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point

  • Antepartum Component: Grade 3 or higher toxicity (for women, also selected Grade 2 hematologic, renal, and hepatic adverse events) [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Postpartum Component: Confirmed presence of infant HIV infection [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
    Defined as HIV NAT positivity of a specimen drawn at any post-randomization visit (i.e., any visit after the Week 1 [Day 6-14] visit), confirmed by HIV NAT positivity of a second specimen drawn at a different time point

  • Postpartum Component: Grade 3 or higher adverse events (for women, also selected Grade 2 hematologic, renal, and hepatic adverse events) [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of progression to AIDS-defining illness or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Obstetrical complications [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Adverse pregnancy outcomes (e.g., stillbirth, preterm delivery at less than 37 weeks gestation, low birth weight less than 2,500 grams, and congenital anomalies) [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Antepartum Component: Infant HIV infection detected by HIV NAT positivity in the birth sample [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Overall and HIV-free infant survival through 24 months of age (in conjunction with infants in the Postpartum Component) [ Time Frame: Measured through 24 months of age ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Adherence to the maternal antiretroviral (ARV) regimen, as measured by maternal report [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Antepartum Component: Maternal and infant viral resistance to the maternal and infant ARV strategies [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Antepartum Component: Cost effectiveness and feasibility of the trial ARV regimens [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Antepartum Component: Maternal HIV RNA less than 400 copies/mL at delivery [ Time Frame: Measured at the time of delivery ] [ Designated as safety issue: No ]
  • Antepartum Component: Antepartum change in HBV DNA viral load between Week 8 and baseline levels (using log HBV DNA) among women with detectable HBV DNA viral loads at baseline and other HBV outcome measures [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
  • Postpartum Component: Infant HIV-free survival through 24 months post-delivery [ Time Frame: Measured through 24 months post-delivery ] [ Designated as safety issue: Yes ]
  • Postpartum Component: Overall infant survival through 12 and 24 months post-delivery [ Time Frame: Measured at 12 and 24 months post-delivery ] [ Designated as safety issue: Yes ]
  • Postpartum Component: Adherence to the maternal and/or infant ARV regimens, as measured by maternal report and hair measures [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Postpartum Component: Rates and patterns of maternal and infant resistance to the maternal and infant ARV regimens [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Postpartum Component: Cost-effectiveness and feasibility of the study ARV prophylaxis regimens [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: AIDS-defining illness [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of progression to AIDS-defining illness, death, or a serious non-AIDS cardiovascular, hepatic, or renal event [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: HIV/AIDS-related events [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Cardiovascular or other metabolic events [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Other targeted medical conditions [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of HIV/AIDS-related event or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of HIV/AIDS-related event or World Health Organization (WHO) Clinical Stage 2 or 3 [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of any condition outlined in Appendix IV of the protocol or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Tuberculosis [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Toxicity: Grade 3 or greater laboratory results or signs and symptoms and selected Grade 2 hematologic, renal, and hepatic laboratory results [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Viral resistance [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Self-reported adherence [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Quality of life [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Changes in plasma concentrations of inflammatory and thrombogenic markers [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Cost-effectiveness [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Postpartum Component: Pharmacokinetic parameters of ARV drugs measured in maternal plasma, hair, breast milk, and infant blood (plasma or dried blood spot) samples collected at birth; Weeks 1, 6, 14, and 26; and subsequent visits during breastfeeding [ Time Frame: Measured through the last study visit during breastfeeding ] [ Designated as safety issue: No ]
  • Postpartum Component: Functional maternal antibody and HIV-envelope binding responses in breast milk and plasma, until cessation of breastfeeding or 18 months postpartum, whichever comes first [ Time Frame: Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first ] [ Designated as safety issue: No ]

Enrollment: 3485
Study Start Date: March 2011
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antepartum: Arm A (Maternal Regimen)
Participants will receive ZDV + sdNVP + TRV.
Drug: Zidovudine (ZDV)
Antepartum Arm A: 300 mg orally twice daily beginning at greater than or equal to 14 weeks gestation (at study entry) through delivery
Drug: Nevirapine (NVP)

For women, 200 mg orally (one single dose) at onset of labor; for infants, oral suspension (dosing according to birth weight) once a day beginning as soon as possible after birth until there is no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever comes first.

Postpartum Arm B infants: NVP age-based daily dosing starting from Week 1 postpartum visit (day 6-14) and continuing for up to 2 weeks after complete breastfeeding cessation or completion of follow up, whichever comes first.

Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Postpartum Arm A: 200 mg/300 mg orally once daily from Week 1 postpartum visit until completion of followup.

Experimental: Antepartum: Arm B (Maternal Regimen)
Participants will receive 3TC-ZDV + LPV-RTV.
Drug: Lamivudine-Zidovudine (3TC-ZDV)
Antepartum Arm B: 150 mg/300 mg orally twice daily beginning at greater than or equal to 14 weeks gestation (at study entry) through delivery and until 1 week postpartum visit (up to 14 days)
Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: A daily dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: dailly dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Postpartum Arm A: a total daily dose of 800 mg/200 mg orally twice daily from Week 1 postpartum visit until completion of followup.

Experimental: Antepartum: Arm C (Maternal Regimen)
Participants will receive TRV + LPV-RTV.
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Postpartum Arm A: 200 mg/300 mg orally once daily from Week 1 postpartum visit until completion of followup.

Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: A daily dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: dailly dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Postpartum Arm A: a total daily dose of 800 mg/200 mg orally twice daily from Week 1 postpartum visit until completion of followup.

Experimental: Antepartum: Infant Prophylaxis Regimen
All infants in the antepartum part of the study will receive NVP each day through 42 days of age or until the Week 6 study visit, whichever is later, regardless of the mother's study arm assignment.
Drug: Nevirapine (NVP)

For women, 200 mg orally (one single dose) at onset of labor; for infants, oral suspension (dosing according to birth weight) once a day beginning as soon as possible after birth until there is no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever comes first.

Postpartum Arm B infants: NVP age-based daily dosing starting from Week 1 postpartum visit (day 6-14) and continuing for up to 2 weeks after complete breastfeeding cessation or completion of follow up, whichever comes first.

Experimental: Postpartum: Arm A (Maternal Regimen)
Women will receive LPV-RTV plus TRV from the Week 1 postpartum visit through the end of maternal follow-up (2 to 5 years). Infants will receive NVP once a day through 6 weeks (42 days) of age.
Drug: Nevirapine (NVP)

For women, 200 mg orally (one single dose) at onset of labor; for infants, oral suspension (dosing according to birth weight) once a day beginning as soon as possible after birth until there is no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever comes first.

Postpartum Arm B infants: NVP age-based daily dosing starting from Week 1 postpartum visit (day 6-14) and continuing for up to 2 weeks after complete breastfeeding cessation or completion of follow up, whichever comes first.

Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Postpartum Arm A: 200 mg/300 mg orally once daily from Week 1 postpartum visit until completion of followup.

Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: A daily dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: dailly dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Postpartum Arm A: a total daily dose of 800 mg/200 mg orally twice daily from Week 1 postpartum visit until completion of followup.

Experimental: Postpartum: Arm B (Infant Regimen)
Infants will receive NVP from 6 (up to 14) days of age until there is no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever comes first.
Drug: Nevirapine (NVP)

For women, 200 mg orally (one single dose) at onset of labor; for infants, oral suspension (dosing according to birth weight) once a day beginning as soon as possible after birth until there is no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever comes first.

Postpartum Arm B infants: NVP age-based daily dosing starting from Week 1 postpartum visit (day 6-14) and continuing for up to 2 weeks after complete breastfeeding cessation or completion of follow up, whichever comes first.

Experimental: Maternal Health: Arm A (Continue triple ARV regimen)
Participants will continue receiving the triple ARV regimen (TRV + LPV-RTV).
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Postpartum Arm A: 200 mg/300 mg orally once daily from Week 1 postpartum visit until completion of followup.

Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: A daily dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: dailly dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); daily dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; daily dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Postpartum Arm A: a total daily dose of 800 mg/200 mg orally twice daily from Week 1 postpartum visit until completion of followup.

No Intervention: Maternal Health: Arm B (Discontinue triple ARV regimen)
Participants will discontinue the triple ARV regimen.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Antepartum Component Inclusion Criteria (Step 1):

  • Confirmed HIV-1 infection, defined as documented positive results from two samples collected at different timepoints prior to study entry. More information on this criterion can be found in the protocol.
  • Currently pregnant and greater than or equal to 14 weeks gestation based on clinical or other obstetrical measurements
  • CD4 count greater than or equal to 350 cells/mm^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm^3), on a specimen obtained within 30 days prior to study entry
  • Results of HBV screening (HBsAg testing) available from specimen obtained within 30 days prior to study entry
  • The following laboratory values from a specimen obtained within 30 days prior to study entry:

    1. Hemoglobin greater than or equal to 7.5 g/dL
    2. White blood cell count (WBC) greater than or equal to 1,500 cells/mm^3
    3. Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
    4. Platelets greater than or equal to 50,000 cells/mm^3
    5. Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN)
    6. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
  • Plans to deliver in the study-affiliated clinic or hospital
  • Has no plans to move outside of the study site area during the 24 months following delivery
  • Age of legal majority for the respective country and willing and able to provide written informed consent
  • Intends to breastfeed

Antepartum Component Exclusion Criteria (Step 1):

  • Participation in PROMISE for a prior pregnancy
  • Ingestion of any antiretroviral (ARV) regimen with three or more drugs (regardless of duration) or more than 30 days of a single or dual ARV regimen during current pregnancy, according to self report or available medical records
  • Requires triple ARV therapy (HAART) for own health based on local standard guidelines
  • World Health Organization (WHO) stage 4 disease
  • Prior receipt of HAART for maternal treatment indications (e.g., CD4 less than 350 cells/mm^3 or clinical indications); however, could have received ARVs for the sole purpose of prevention of mother-to-child transmission (PMTCT) in previous pregnancies (prior PMTCT regimens could have included a triple ARV regimen, ZDV, 3TC-ZDV, and/or sdNVP for PMTCT, as well as use of a short dual nucleoside reverse transcriptase inhibitor [NRTI] "tail" to reduce risk of NVP resistance.)
  • In labor - at onset or beyond (may be eligible for the Late Presenter registration)
  • Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
  • Current or history of tuberculosis (TB) disease (positive PPD without TB disease is not exclusionary)
  • Use of prohibited medications within 14 days prior to study entry (refer to the protocol for a list of prohibited medications)
  • Fetus detected to have serious congenital malformation (ultrasound not required to rule out this condition)
  • Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block [also known as Mobitz I or Wenckebach] is not considered exclusionary)
  • Known to meet the local standard criteria for treatment of HBV (Note: HBV DNA testing or other specialized assessments are not expected to be performed as part of this study. A woman would be excluded only if this information is documented from other sources and she meets the local standard criteria for HBV treatment based on those assessments.)
  • Social or other circumstances that would hinder long-term follow-up, in the opinion of the site investigator
  • Currently incarcerated

Antepartum Component Inclusion Criteria (Step 2):

  • On Antepartum Step 1 Arm A (ZDV + sdNVP + TRV tail); OR on Antepartum Step 1 Arm B or C (maternal triple ARV prophylaxis) and currently receiving triple ARV prophylaxis but does not meet the criteria for switching to a second line regimen and Step 3 entry; OR on Antepartum Step 1 Arm B or C (maternal triple ARV prophylaxis) and is not enrolled in the Postpartum Component or Maternal Health Component but remains in the observational follow-up and is not currently receiving a triple ARV regimen (stopped the regimen)
  • Reached an indication for triple ARV therapy (HAART) for own health, as specified in the protocol
  • Willing and able to initiate HAART

Antepartum Component Exclusion Criteria (Step 2):

  • None

Antepartum Component Inclusion Criteria (Step 3):

  • On Antepartum Step 1 Arm B or C or on Step 2
  • Met the criteria for switching to a second line regimen, as specified in the protocol, while on a triple ARV regimen
  • Willing and able to initiate an alternative triple ARV regimen

Antepartum Component Exclusion Criteria (Step 3):

  • Women on Antepartum Step 1 Arm B or C who were not enrolled in the Postpartum Component or Maternal Health Component but remain in observational follow-up and are not currently receiving a triple ARV regimen

Postpartum Component Inclusion Criteria (Step 1):

  • Participation in the Antepartum Component or registered as a Late Presenter
  • Intent to breastfeed
  • Provided written informed consent
  • Has no plans to move outside of the study site area during the 24 months following delivery
  • Maternal CD4 count greater than or equal to 350 cells/mm^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm^3), from a specimen obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • The following maternal laboratory values within 30 days prior to entry:

    1. Hemoglobin greater than or equal to 7.0 g/dL
    2. WBC greater than or equal to 1,500 cells/mm^3
    3. ANC greater than or equal to 750 cells/mm^3
    4. Platelets greater than or equal to 50,000 cells/mm^3
    5. ALT less than or equal to 2.5 times the upper limit of normal (ULN)
    6. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
  • Infant alive, healthy, less than or equal to 14 days of age, and uninfected (negative HIV NAT result on specimen drawn prior to study entry)
  • The following infant lab values on specimen obtained prior to study entry (within 14 days of birth):

    1. Hemoglobin greater than or equal to 10 g/dL
    2. WBC greater than or equal to 1,500 cells/mm^3
    3. ANC greater than or equal to 750 cells/mm^3
    4. Platelets greater than or equal to 50,000 cells/mm^3
    5. ALT less than or equal to 2.5 times the ULN
  • For Registered Late Presenters: Confirmed maternal HIV-1 infection, defined as documented positive results from two samples collected at different time points at any time prior to entry. More information on this criterion can be found in the protocol.

Postpartum Component Exclusion Criteria (Step 1):

  • Positive infant HIV NAT result on specimen drawn prior to entry or no infant HIV NAT result on specimen drawn prior to entry
  • Life-threatening infant illness or birth condition incompatible with life
  • Infant birth weight less than 2.0 kg
  • Social or other circumstances that would hinder long-term follow-up, as judged by the site investigator
  • Current or history of TB disease (positive PPD without TB disease is not exclusionary)
  • Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block [also known as Mobitz I or Wenckebach] is not considered exclusionary)
  • Requires triple ARV therapy (HAART) for own health (includes women who are on Step 2 of the Antepartum Component and women who are on Step 3 of the Antepartum Component for immunologic/clinical disease progression requiring a change in their triple ARV regimen). Note: Women on Step 3 of the Antepartum Component who were never on Step 2 and who entered Step 3 for toxicity or virologic failure without clinical or immunologic disease progression requiring a complete change in the triple ARV regimen are eligible for the Postpartum Component.

Postpartum Component Inclusion Criteria (Step 2):

  • On Step 1 Arm B (infant prophylaxis); OR on Step 1 Arm A (maternal prophylaxis) and currently receiving triple ARV prophylaxis but does not meet the criteria for switching to a second line regimen and entry into Step 3; OR on Step 1 Arm A (maternal prophylaxis) and not enrolled in the Maternal Health Component but remains in observational follow-up and is not currently receiving a triple ARV regimen (stopped the regimen)
  • Reached an indication for triple ARV therapy (HAART), as specified in the protocol
  • Willing and able to initiate HAART

Postpartum Component Exclusion Criteria (Step 2):

  • None

Postpartum Component Inclusion Criteria (Step 3):

  • On Step 1 Arm A or on Step 2
  • Met the criteria for switching to a second line regimen, as specified in the protocol, while on a triple ARV regimen
  • Willing and able to initiate an alternate triple ARV regimen

Postpartum Component Exclusion Criteria (Step 3):

  • On Step 1 Arm A and was not enrolled in the Maternal Health Component but remains in observational follow-up and is not currently receiving a triple ARV regimen

Maternal Health Component Inclusion Criteria (Step 1):

  • Randomly assigned to triple ARV prophylaxis as part of the Postpartum Component and has continued triple ARV prophylaxis until the current randomization without treatment interruption (defined as more than 14 consecutive days of missed dosing) within the previous 30 days; OR randomly assigned to triple ARV prophylaxis in the Antepartum Component but ineligible for the Postpartum Component and has continued triple ARV prophylaxis until the current randomization without treatment interruption (defined as more than 7 consecutive days of missed dosing) within the previous 30 days
  • Within 8 weeks after complete breastfeeding cessation is achieved (defined as completely stopping all exposure to breast milk for greater than or equal to 28 days); i.e., within 29 to 84 days of last breast milk exposure, or reached 18 months postpartum (whichever comes first). Women who reach 18 months postpartum while still breastfeeding will be eligible for entry within 2 weeks before and 4 weeks after the Week 74 visit (Week 72-78); OR if the woman was randomized to triple ARV prophylaxis in the Postpartum Component and her infant is infected and still breastfeeding, she will be eligible for the Maternal Health Component within 42 days of specimen collection for the confirmatory infant HIV NAT; OR if the woman was randomized to triple ARV prophylaxis in the Antepartum Component but mother-infant pair was ineligible for the Postpartum Component she will be eligible for the Maternal Health Component beginning at the Week 1 visit (6-14 days postpartum) through 28 days after delivery; these women should be randomized as soon as possible, ideally within 6-14 days after delivery; OR if the woman was randomized to triple ARV prophylaxis in the Postpartum Component and breastfeeding risk for MTCT ceases for other reasons (e.g., infant death or permanent removal from home through legal services or adoption) within 28 days of event. More information on this criterion can be found in the protocol.
  • Provided written informed consent
  • CD4 cell count greater than or equal to 350 cells/mm^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm^3), on a specimen obtained within 30 days prior to study entry
  • The following laboratory values on a specimen obtained within 30 days prior to study entry:

    1. ANC greater than or equal to 750 cells/mm^3
    2. Hemoglobin greater than or equal to 7.0 gm/dL
    3. Platelet count greater than or equal to 50,000 cells/mm^3
    4. ALT (SGPT) less than or equal to 2.5 times the ULN
    5. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
  • Intend to remain in current geographical area of residence for the duration of study

Maternal Health Component Exclusion Criteria (Step 1):

  • WHO Stage 4 disease
  • Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
  • Current or history of TB disease (positive PPD without TB disease is not exclusionary)
  • Use of prohibited medications within 14 days prior to study entry
  • Social or other circumstances that would hinder long term follow-up as judged by the site investigator
  • Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block [also known as Mobitz I or Wenckebach] is not considered exclusionary)
  • Requires a triple ARV regimen for own health (includes women who are on Step 2 of the Antepartum Component or the Postpartum Component and women who are on Step 3 of the Antepartum Component or the Postpartum Component who entered Step 3 for immunologic/clinical disease progression requiring a change in their triple ARV regimen [HAART]).

Maternal Health Component Inclusion Criteria (Step 2):

  • On Step 1 Arm B (discontinue the study triple ARV regimen arm); OR on Step 1 Arm A (triple ARV regimen) and currently on the triple ARV regimen but does not meet the criteria for switching to a second line regimen and entry into Step 3
  • Reached an indication for triple ARV treatment for own health, as specified in the protocol
  • Willing and able to re-initiate or continue triple ARV therapy

Maternal Health Component Exclusion Criteria (Step 2):

  • None

Maternal Health Component Inclusion Criteria (Step 3):

  • On Step 1 Arm A or Step 2
  • Meets the criteria for switching to a second line regimen, as specified in the protocol, while on a triple ARV regimen
  • Willing and able to initiate an alternate triple ARV regimen (HAART)

Maternal Health Component Exclusion Criteria (Step 3):

  • On Step 1 Arm B
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01061151

Locations
India
Byramjee Jeejeebhoy Medical College (BJMC) CRS
Pune, Maharashtra, India, 411001
Malawi
Blantyre CRS
Blantyre, Malawi
Malawi CRS
Lilongwe, Malawi
South Africa
Soweto IMPAACT CRS
Johannesburg, Gauteng, South Africa, 1862
Shandukani CRS
Johannesburg, Gauteng, South Africa, 2001
Durban Paediatric HIV CRS
Durban, KwaZulu-Natal, South Africa, 4001
Umlazi CRS
Durban, KwaZulu-Natal, South Africa, 4001
Family Clinical Research Unit (FAM-CRU) CRS
Tygerberg, Western Cape Province, South Africa, 7505
Tanzania
Kilimanjaro Christian Medical Centre (KCMC)
Moshi, Tanzania
Uganda
MU-JHU Research Collaboration CRS
Kampala, Uganda
Zambia
George CRS
Lusaka, Zambia
Zimbabwe
Seke North CRS
Chitungwiza, Zimbabwe
St. Mary's CRS
Chitungwiza, Zimbabwe
Parirenyatwa CRS
Harare, Zimbabwe
Sponsors and Collaborators
Investigators
Study Chair: Mary Glenn Fowler, MD, MPH Johns Hopkins Medical Institute, Makerere U.-JHU Research Collaboration
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01061151     History of Changes
Other Study ID Numbers: 1077BF (PROMISE), 10777, IMPAACT 1077BF
Study First Received: February 1, 2010
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Lamivudine, zidovudine drug combination
Lopinavir
Tenofovir
Tenofovir disoproxil
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on October 22, 2014