Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries - Full Text View

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Birth Weight Breast Feeding HIV/AIDS HIV/AIDS and Pregnancy Postpartum Care

Drug Information available for: Zidovudine Nevirapine Lamivudine Emtricitabine Tenofovir Ritonavir Lopinavir Tenofovir Disoproxil Fumarate Truvada

U.S. FDA Resources

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 ]

Estimated Enrollment:	5900
Study Start Date:	March 2011
Estimated Primary Completion Date:	January 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 with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2,499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later. 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)
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: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days). Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).
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) Drug: Lopinavir-ritonavir (LPV-RTV) Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days). Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).
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 with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2,499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later.
Experimental: Postpartum: Arm A (Maternal Regimen) Women will receive LPV-RTV plus TRV from 6 (up to 14) days postpartum through the end of breastfeeding or through 18 months postpartum, whichever comes first. 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 with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2,499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later. 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) Drug: Lopinavir-ritonavir (LPV-RTV) Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days). Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).
Experimental: Postpartum: Arm B (Infant Regimen) Infants will receive NVP once a day from 6 (up to 14) days of age through the end of breastfeeding or through 18 months postpartum, whichever comes first.	Drug: Nevirapine (NVP) For women, 200 mg orally (one single dose) at onset of labor; for infants with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2,499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later.
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) Drug: Lopinavir-ritonavir (LPV-RTV) Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days). Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).
No Intervention: Maternal Health: Arm B (Discontinue triple ARV regimen) Participants will discontinue the triple ARV regimen.

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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 7 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 2 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 29-42 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

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

Locations

India
BJ Medical College CRS	Recruiting
Pune, Maharashtra, India, 411001
Contact: Nishi Suryavanshi, PhD 91-20-26052419 nishi@jhumitpune.com
Malawi
College of Med. JHU CRS	Recruiting
Blantyre, Malawi
Contact: Leslie Degnan 265-888-208609 ldegnan@jhsph.edu
University of North Carolina Lilongwe CRS	Recruiting
Lilongwe, Malawi
Contact: Mina C. Hosseinipour, MD 265-1758938 minach@med.unc.edu
South Africa
Soweto IMPAACT CRS	Recruiting
Johannesburg, Gauteng, South Africa
Contact: Nasreen Abrahams 27-11-9899742 abrahamsn@phru.co.za
Shandukani Research CRS	Recruiting
Johannesburg, Gauteng, South Africa, 2001
Contact: Hermien Gous, PharmD 27-11-3585500 ext 5930 hgous@wrhi.ac.za
Durban Paediatric HIV CRS	Recruiting
Durban, KwaZulu-Natal, South Africa, 4001
Contact: Rosie Mngqibisa, MBBS 27-31-2604669 mngqibisa@ukzn.ac.za
CAPRISA Umlazi CRS	Recruiting
Umlazi, KwaZulu-Natal, South Africa, 4066
Contact: Vani Chetty 27-31-2604680 Chettyv1@ukzn.ac.za
Stellenbosch Univ. CRS	Recruiting
Cape Town, South Africa, 7505
Contact: Joan Coetzee 27-21-9384157 joan@sun.ac.za
Tanzania
Kilimanjaro Christian Medical CRS	Recruiting
Moshi, Tanzania
Contact: Cynthia A. Asiyo 255-27-2754086 casiyo@gmail.com
Uganda
Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS	Recruiting
Kampala, Uganda
Contact: Carolyne Onyango, MD 256-414-541044 carolonyango@mujhu.org
Zambia
George Clinic CRS	Recruiting
Lusaka, Zambia
Contact: Felistas Mbewe 260-966828341 felistas.mbewe@cidrz.org
Zimbabwe
Seke North CRS	Recruiting
Chitungwiza, Zimbabwe
Contact: Suzen Maonera 263-912288160 suzen@uz-ucsf.co.zw
St. Mary's CRS	Recruiting
Chitungwiza, Zimbabwe
Contact: Francis Jaji 263-912268516 francis@uz-ucsf.co.zw
UZ-Parirenyatwa CRS	Recruiting
Harare, Zimbabwe
Contact: Jimijika Batani 263-912272818 jbatani@uz-ucsf.co.zw

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Mary Glenn Fowler, MD, MPH

Johns Hopkins Medical Institute, Makerere U.-JHU Research Collaboration

More Information

Publications:

Taha T, Nour S, Li Q, Kumwenda N, Kafulafula G, Nkhoma C, Broadhead R. The Effect of Human Immunodeficiency Virus and Breastfeeding on the Nutritional Status of African Children. Pediatr Infect Dis J. 2010 Jan 5; [Epub ahead of print]

Becquet R, Ekouevi DK, Arrive E, Stringer JS, Meda N, Chaix ML, Treluyer JM, Leroy V, Rouzioux C, Blanche S, Dabis F. Universal antiretroviral therapy for pregnant and breast-feeding HIV-1-infected women: towards the elimination of mother-to-child transmission of HIV-1 in resource-limited settings. Clin Infect Dis. 2009 Dec 15;49(12):1936-45. Review.

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:	November 19, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Lamivudine
Tenofovir

Tenofovir disoproxil
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 14, 2013

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