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CompletedNCT01061151PROMISEUpdated Feb 11, 2022Results posted

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

A Phase 3 interventional study of Zidovudine (ZDV) and Nevirapine (NVP): Antepartum Mothers in HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 14 sites in 7 countries. Per ClinicalTrials.gov, last updated 2022-02-11.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
3,747
Allocation
Randomized
Sex
All
01

Study summary

The purpose of this study was to examine, in an integrated and comprehensive fashion, three critical questions currently facing HIV-infected pregnant and postpartum women and their infants:

  1. What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV?
  2. What is the optimal intervention for the prevention of postpartum transmission in breastfeeding (BF) infants?
  3. What is the optimal intervention for the preservation of maternal health after the risk period for prevention of mother-to-child-transmission ends (either at delivery or cessation of BF)?

The overall PROMISE protocol had three separate interventional components to address each of these three questions and was conducted at locations in Africa and other parts of the world. Due to variations in the standard of care for HIV-infected pregnant and postpartum women and their infants at different sites, not all of these questions were relevant. Therefore, two separate versions of the PROMISE protocol were developed, each containing only the relevant components. The 1077BF protocol was used at sites where the standard method of infant feeding was breastfeeding, whereas the 1077FF protocol was used at sites where the standard method of infant feeding was formula feeding. The analyses were collapsed across the two protocol versions, and therefore the summaries contain the results of the 1077BF and/or the 1077FF protocols.

Read the detailed description

The incidence of mother-to-child transmission (MTCT) of HIV has decreased in recent years in the United States, Europe, and other resource-advantaged countries. Several factors have contributed to this decrease, including the administration of HAART during pregnancy, caesarean section delivery methods, and the use of formula instead of breastfeeding to feed infants. However, in resource-limited countries, the incidence of pediatric HIV infection remains high. Many pregnant women in these countries do not receive an adequate course of HAART, and the majority breastfeed their children.

This study was divided into three components (Antepartum, Postpartum, and Maternal Health Components). The following is a description of each of the three open label sequential randomization components, each designed to address one of the following three main objectives:

  1. Antepartum Component: This PROMISE component compared the safety and efficacy of different HAART regimens for preventing the transmission of HIV during pregnancy, labor, and delivery.

    • Participants were randomly assigned to one of the following three arms:

    • Maternal Regimens:

      • Arm A : 1) Zidovudine (ZDV) from study entry through delivery, 2) single dose nevirapine (sdNVP) and emtricitabine-tenofovir disoproxil (TRV ) intrapartum, and 3) TRV postpartum for up to 14 days post-partum. Arm A is also labeled as ZDV+sdNVP+TRV tail.
      • Arm B: Lamivudine (3TC)-zidovudine (ZDV) + lopinavir (LPV)-ritonavir (RTV) from study entry up to 14 days postpartum. Arm B is also labeled as 3TC-ZDV/LPV-RTV.
      • Arm C: TRV/LPV-RTV from study entry up to 14 days postpartum. Arm C is also labeled as FTC-TDF/LPV-RTV.
    • All infants born to women enrolled in this study were to receive NVP once a day as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever was later. Women switched or initiated HAART if it was needed for their own health.
    • During pregnancy, participants attended study visits at study entry, 2 and 4 weeks after entry, and then every 4 weeks until labor and delivery. Women and infants were monitored during labor and delivery and attended a study visit 6 to 14 days after delivery. After delivery, eligibility criteria were assessed for subsequent randomizations (either Postpartum or Maternal Health). If they failed the entry criteria for the subsequent randomization, the mothers remained in follow-up for safety assessments and the infants were followed until the 104 week visit; otherwise they were followed under the subsequent component.
    • All three antepartum arms were not available to all women throughout the PROMISE study. When the trial began, there were limited safety data on tenofovir in pregnancy, and randomization to tenofovir-based ART was limited to women coinfected with HIV and HBV, because benefit was felt to outweigh risk in that group. During period 1 (PROMISE protocol version 2.0 - April 2011 through September 2012), women without HBV coinfection were randomized to either Arm A or Arm B; and Hepatitis B (HBV) co-infected women were randomized to either Arm A, Arm B, or Arm C. However, in October 2012, with increased data on tenofovir in pregnancy, the protocol was modified to allow women regardless of HBV status to be assigned to any of the three regimens during period 2 (PROMISE protocol version 3.0 - October 2012 through the end of antepartum enrollment on October 1, 2014). By arm comparisons were restricted to times in which there were contemporaneous randomizations.
    • Late Presenters: In addition the Antepartum Component, participants could enter PROMISE through the Late Presenters Registration (LP). Late presenters were identified in early or active labor or in the immediate postpartum period (up to 5 days postpartum). The Late Presenters Registration facilitated a structure to screen women and infants for randomization in the Postpartum Component. Women and infants not randomized in the Postpartum Component of PROMISE were followed through the Week 6 visit.
    • There were 3543 mothers and 3407 live born infants enrolled in the Antepartum Component. There were 204 mothers and 204 live born infants in the Late Presenters Registration.

  2. Postpartum Component: This PROMISE component compared the safety and efficacy of maternal triple ARV prophylaxis versus daily infant NVP prophylaxis for the prevention of mother-to-child transmission (PMTCT) through breastfeeding. The Postpartum Component consisted of mothers and infants from the Antepartum Component and the Late Presenters Registration who passed the Postpartum Component entry criteria.

    • Participants were randomly assigned to one of two arms:

      • Arm A: Women received LPV-RTV plus TRV from the Week 1 postpartum visit through the end of maternal follow-up (2 to 5 years). Infants received NVP once a day through 42 days of age or until the Week 6 study visit, whichever was later.
      • Arm B: Infants received NVP once a day from the Week 1 postpartum visit until the end of risk for MTCT or until 18 months postpartum (104 weeks). Women did not receive antiretroviral drugs for MTCT prophylaxis.
    • The maternal study visits were at entry, at postpartum weeks 6, 14, 26, and every 12 weeks thereafter. Infant study visits were at entry, every 4 weeks between postpartum weeks 6-26, every 12 weeks between postpartum week 38-98, and at postpartum week 104. At the end of risk for MTCT or 18 months postpartum, the mothers' eligibility criteria were assessed for a subsequent randomization in the Maternal Health Component. If they did not meet entry criteria for the Maternal Health randomization, they remained in follow-up for safety assessments; otherwise they were followed under the Maternal Health Component. Infants were followed until the 104 week visit.
    • Women switched or initiated HAART if it was needed for their own health. If a woman in Arm B initiated HAART then her infant discontinued NVP after 12 weeks of HAART or after her viral load was suppressed, whichever came first.
    • There were 2431 mothers and 2444 infants randomized as part of the Postpartum Component.

  3. Maternal Health Component: This PROMISE component randomized women to continue or discontinue HAART after the end of risk for MTCT, either after delivery or after breastfeeding. Participants included women who were receiving the triple ARV regimen in the Postpartum Component; or receiving the triple ARV regimen in the Antepartum Component and were ineligible for the Postpartum Component.

    • Participants were randomly assigned to one of two study arms:

      • Arm A: Participants continued to receive the triple ARV regimen (preferred regimen was LPV-RTV plus TRV).
      • Arm B: Participants discontinued the triple ARV regimen.
    • Study visits occurred at Weeks 4 and 12 and then every 3 months thereafter. Study visits included a medical history review, questionnaires, physical exam, and blood collection. Women switched or initiated a triple ARV regimen if it was needed for their own health.
    • There were 875 mothers randomized as part of the Maternal Health Component.

    • The analyses for the Maternal Health Component we not solely based on the Maternal Health Randomization. Instead there were four prespecified comparison groups for the Maternal Health Component. The four comparison groups used the three randomizations as appropriate to answer the following questions:

      • Question 1: What is the effect on women of using a maternal triple ARV regimen to prevent MTCT during pregnancy, relative to using ZDV + sdNVP + TRV tail to prevent MTCT during pregnancy?
      • Question 2: What is the effect on women of using a maternal triple ARV regimen to prevent MTCT during breastfeeding, relative to using infant NVP to prevent MTCT during breastfeeding?
      • Question 3: What is the effect on women of extending versus discontinuing the antepartum/intrapartum maternal triple ARV regimen at the time of birth?
      • Question 4: What is the effect on women of extending versus discontinuing the postpartum maternal triple ARV regimen after the cessation of risk for MTCT during breastfeeding?
    • There were 1602 mothers included in the analyses for Question 2.

PROMISE mothers were followed for 2 to 5 years, depending on when they enrolled. Infants were followed up to 104 weeks of age. Infant and maternal follow-up ended in September 2016. PROMISE randomizations were halted in the summer of 2014 due to slow accrual to the Later Presenters Registration and the Formula Feeding protocol. Due to the results of an external study, on July 7th 2015 the PROMISE interventions were halted and ART was offered to all participants. Per recommendation from the Data and Safety and Monitoring Board on November 4th 2014, the primary analyses for the Antepartum Component include follow-up through September 10th, 2014. Per recommendation from the Data and Safety and Monitoring Board on November 12th 2015, the primary analyses for the Postpartum Component include follow-up through July 7th, 2015. The Adverse Events in the Reported Adverse Event section include all study follow-up.

02

Conditions studied

  • HIV Infections

Keywords

  • Mother to Child Transmission
  • HIV Infection
  • HAART
  • Maternal Health
  • Breastfeeding
  • Perinatal transmission
03

In context

HIV Infections

4,340 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 3,747 is above the median of 83 across 3,312 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.

Browse National Institute of Allergy and Infectious Diseases (NIAID) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Antepartum Component Inclusion Criteria:

  • Confirmed HIV-1 infection, defined as documented 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.
  • 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

Antepartum Component Exclusion Criteria:

  • 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

Late Presenter Inclusion Criteria:

  • Age of legal majority for the respective country
  • HIV-1 infection, defined as documented positive results from tests performed on one sample at any time prior to Late Presenter Registration
  • In labor (from onset/early labor or beyond) or within 5 days after delivery (with day of delivery considered day 0)
  • Has provided written informed consent
  • Has no plans to move outside of the study site area during the 24 months following delivery
  • If delivered, infant alive and healthy (In the case of a multiple birth, a mother-infant pair will be included in the Late Presenter registration only if both/all infants and the mother meet the eligibility criteria. If only one infant of a multiple birth is alive, the M-I pair may be registered if the infant and the mother otherwise meet all of the eligibility criteria.)

Late Presenter Exclusion Criteria:

  • Participation in PROMISE in prior pregnancy
  • Ingestion of any antiretroviral regimen during current pregnancy (including for solely for PMTCT), according to self report and available medical records (Note: Use of ARVs provided as standard of care for PMTCT during labor/delivery or postpartum prior to Late Presenter registration is not exclusionary.)
  • If known: CD4 count \< 350 cells/mm3 or below the country-specific threshold for initiation of treatment, if that threshold is > 350 cells/mm3, on specimen obtained within 30 days prior to study entry (result not required prior to registration)
  • Requires triple ARV therapy (HAART) for own health according to local standard guidelines
  • WHO Stage 4 disease
  • Prior receipt of HAART for maternal treatment indications (e.g., CD4 \< 350 cells/mm3 or clinical indications); however, could have received ARVs for the sole purpose of PMTCT in previous pregnancies. (Prior PMTCT regimens could have included a triple ARV regimen, ZDV, 3TCZDV and/or sdNVP for PMTCT, as well as use of a short dual NRTI "tail" to reduce risk of NVP resistance.)
  • Current or history of TB disease (positive PPD without TB disease is not exclusionary)
  • Known positive infant HIV nucleic acid test (NAT) result (result not required prior to registration)
  • Fetal demise or early neonatal death (prior to enrollment/registration)
  • Fetus detected with serious congenital malformation (ultrasound not required to rule out this condition)
  • Life threatening infant illness or birth condition incompatible with life
  • If delivered, infant birth weight \< 2.0 kg
  • Social or other circumstances which would hinder long-term follow-up, in the opinion of 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)

Postpartum Component Inclusion Criteria:

  • Participation in the Antepartum Component or registered as a Late Presenter
  • 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:

  • 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

Maternal Health Component Inclusion Criteria:

  • 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 two 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 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:

  • 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
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Investigator, Outcomes assessor)
Enrollment
3,747 participants (actual)

Study arms

  • Active comparator
    Antepartum Arm A

    Mothers received ZDV + sdNVP + TRV Tail

    Drug: Zidovudine (ZDV) · Drug: Nevirapine (NVP): Antepartum Mothers · Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail · Drug: Nevirapine (NVP): Infant short-course

  • Experimental
    Antepartum Arm B

    Mothers received Triple ARV (3TC-ZDV + LPV-RTV)

    Drug: Lamivudine-Zidovudine (3TC-ZDV) · Drug: Lopinavir-ritonavir (LPV-RTV) · Drug: Nevirapine (NVP): Infant short-course

  • Experimental
    Antepartum Arm C

    Mothers received Triple ARV (TRV + LPV-RTV)

    Drug: Lopinavir-ritonavir (LPV-RTV) · Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) · Drug: Nevirapine (NVP): Infant short-course

  • Other
    Late Presenters

    Registration to facilitate a structure to screen women and infants for randomization in the Postpartum Component.

    Other: No Intervention

  • Experimental
    Postpartum Arm A (Maternal Prophylaxis)

    Mothers received prophylaxis \[preferred regimen: TRV + LPV-RTV\]. Infants received short-course NVP.

    Drug: Lopinavir-ritonavir (LPV-RTV) · Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) · Drug: Nevirapine (NVP): Infant short-course

  • Experimental
    Postpartum Arm B (Infant Prophylaxis)

    Infants received extended NVP.

    Drug: Nevirapine (NVP): Infant extended

  • Experimental
    Maternal Health Arm A (Continue triple ARVs)

    Mothers continued receiving triple ARV regimen \[preferred regimen: TRV + LPV-RTV\].

    Other: Continue triple ARVs

  • Active comparator
    Maternal Health Arm B (Discontinue triple ARVs)

    Mothers discontinued triple ARV regimen.

    Other: Discontinue triple ARVs

Interventions

  • DrugZidovudine (ZDV)

    300 mg twice daily

  • DrugNevirapine (NVP): Antepartum Mothers

    200 mg at onset of labor

  • DrugEmtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail

    200 mg/300 mg x 2 tablets at onset of labor or as soon as possible thereafter; 200 mg/300 mg orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

  • DrugLamivudine-Zidovudine (3TC-ZDV)

    150 mg/300 mg twice daily

  • DrugLopinavir-ritonavir (LPV-RTV)

    400 mg/100 mg twice daily beginning at \>= 14 weeks gestation; 600 mg/150 mg twice daily beginning at \>= 28 weeks gestation or at next visit (during third trimester) through delivery; 400 mg/100 mg twice daily after delivery up to 14 days postpartum.

  • DrugEmtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

    200 mg/300 mg

  • DrugNevirapine (NVP): Infant short-course

    Oral suspension (dosing according to birth weight) once a day through 42 days of age or through the week 6 visit, whichever is later.

  • DrugNevirapine (NVP): Infant extended

    Oral suspension (dosing according to birth weight) once a day from 6 (up to 14) days of age until there was no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever came first.

  • OtherNo Intervention

    Women registered before/during labor received the full Antepartum Arm A regimen. Women registered after labor, and who received nevirapine outside of the study, received the Emtricitabine-tenofovir disoproxil fumarate (Truvada \[TRV\]) tail.

  • OtherDiscontinue triple ARVs

    ARVs were discontinued. When protocol specified criteria were met, mothers could be prescribed any licensed antiretroviral medication, as long as the treatment met the definition of HAART (three ARV drugs from two or more drug classes).

  • OtherContinue triple ARVs

    Mothers could be prescribed any licensed antiretroviral medication, as long as the treatment met the definition of HAART (three ARV drugs from two or more drug classes).

06

What researchers measure

Primary outcomes

  1. Antepartum Component: Number of Confirmed Infant HIV Infections

    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

    Time frame: Measured at birth or Week 1 study visit

  2. Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events

    These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

    Time frame: Measured through the Week 1 postpartum study visit

  3. Antepartum Component: Number of Mothers With Obstetrical Complications

    Complications included deaths, diagnoses, signs/symptoms, chemistry lab tests, or hematological lab tests, with grades of 3 (Severe) or worse. Obstetrical complications were those classified by the MedDra coding system as "Pregnancy, puerperium and perinatal conditions", except if the condition was the death of the fetus: "Abortions not specified as induced or spontaneous", "Abortions spontaneous", or "Stillbirth and foetal death."

    Time frame: Measured through the Week 1 postpartum study visit

  4. Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies)

    Composite outcome

    Time frame: Measured at birth

  5. Postpartum Component: Incidence of Confirmed Infant HIV Infection

    Defined as infant 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. Analyses were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.

    Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first

  6. Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events

    These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

    Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first

  7. Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death

    AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses in Appendix IV of the protocol. These events were reviewed and confirmed by an Endpoint review group.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

Secondary outcomes

  1. Antepartum Component: Number of Infant HIV Infections

    Detected by HIV NAT positivity

    Time frame: Measured at the birth (<= 3 days postpartum) visit

  2. Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component)

    For overall survival, failure was defined to be death. For HIV-free survival, failure was defined to be either death or developing HIV. The probability of living, or living without HIV infection, at 104 weeks was calculated by Kaplan-Meier estimation of the survival function.

    Time frame: Measured from birth through 104 weeks of age

  3. Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery

    Analysis used the principle of intent to treat.

    Time frame: Measured at the time of delivery

  4. Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery

    Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit, confirmed by HIV NAT positivity of a second specimen drawn at a different time point, or infant death. Analyses (Kaplan-Meier probabilities) were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.

    Time frame: Measured through 24 months post-delivery

  5. Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery

    Analyses (Kaplan-Meier probabilities) conducted for all individual infants (rather than M-I pair)

    Time frame: Measured at 12 and 24 months post-delivery

  6. Maternal Health Component: Incidence of Death

    Number of women who died during the maternal health component; that is, who had been randomized to either continue or discontinue ART after risk of HIV vertical transmission through breastfeeding was over.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  7. Maternal Health Component: Incidence of AIDS-defining Illness

    "AIDS-defining illness" refers to the WHO Clinical Stage 4 illnesses listed in Appendix IV. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  8. Maternal Health Component: Incidence of HIV/AIDS-related Events

    "HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  9. Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events

    Cardiovascular or metabolic events of particular concern were included in this analysis. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Metabolic events considered were diabetes mellitus, lipodystrophy, or dyslipidemia. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  10. Maternal Health Component: Other Targeted Medical Conditions

    Other (non-cardiologic) medical conditions of particular concern were included in this outcome. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Events included were metabolic events, hepatic events, renal events, infections such as pulmonary tuberculosis, malaria, or other serious bacterial infections, and others.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  11. Maternal Health Component: Incidence of HIV/AIDS-related Event or Death

    "HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  12. Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events

    "HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  13. Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern

    Particular events were targeted as those of particular concern. This outcome considered all such events: death, events defining WHO stages II, III, or IV, targeted cardiovascular adverse events, other targeted adverse events, or cancers which were not AIDS-defining. A complete list can be found in Appendix IV of the Protocol. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  14. Maternal Health Component: Incidence of Tuberculosis

    Incidence of tuberculosis.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  15. Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results

    The maternal safety endpoints summarized include grade 2, 3 or 4 hematologies (hemoglobin (Hb), White Blood Cells (WBC), Absolute Neutrophil Count (ANC), platelet count), chemistries (Alanine Aminotransferase (ALT or SGPT), serum creatinine), and grade 3 or 4 signs and symptoms that occurred post-randomization. These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

  16. Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event

    This outcome included AIDS-defining illnesses or cardiovascular, hepatic, or renal adverse events of particular concern which were evaluated as serious. Serious outcomes were both those defined as serious according to the International Conference on Harmonization (ICH) definition, or outcomes with grades equal to or worse than 3 ("Severe"). A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy. Hepatic events considered were cirrhosis and idiopathic sclerosing cholangitis. Renal events considered were renal insufficiency, acute or chronic.

    Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

Other outcomes

  1. Maternal Health Component: Cost-effectiveness

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.

    Time frame: From study entry until July 7, 2015.

  2. Maternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since inflammation and thrombogenic markers were not a focus of the study.

    Time frame: From study entry until July 7, 2015.

  3. Maternal Health Component: Quality of Life

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since quality of life was not a focus of the study.

    Time frame: From study entry until July 7, 2015.

  4. Maternal Health Component: Self-reported Adherence

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.

    Time frame: From study entry until July 7, 2015.

  5. Maternal Health Component: Viral Resistance

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.

    Time frame: From study entry until July 7, 2015.

  6. 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

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since functional maternal antibody and HIV-envelope binding responses were not a focus of the study.

    Time frame: Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first

  7. 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

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since pharmacokinetics was not a focus of the study.

    Time frame: Measured through the last study visit during breastfeeding, or 18 months postpartum, whichever comes first

  8. Postpartum Component: Cost-effectiveness and Feasibility of the Study ARV Prophylaxis Regimens

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.

    Time frame: Measured at the end of the 5-year study period

  9. Postpartum Component: Rates and Patterns of Maternal and Infant Resistance to the Maternal and Infant ARV Regimens

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.

    Time frame: Measured at the end of the 5-year study period

  10. Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures

    Adherence is by maternal report; adherence through hair analysis is not included here. The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.

    Time frame: Week 6 visit (14 days - 9 weeks postpartum); Week 14 visit (10-19 weeks postpartum); Week 26 visit (20 to 31 weeks postpartum); Week 50 visit (44 to 55 weeks postpartum); and Week 74 visit (68 to 80 weeks postpartum).

  11. 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

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since changes in HBV DNA Viral Load was not a focus of the study.

    Time frame: Measured at Week 8

  12. Antepartum Component: Cost Effectiveness and Feasibility of the Trial ARV Regimens

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since cost effectiveness was not a focus of the study.

    Time frame: Measured at the end of the 5-year study period

  13. Antepartum Component: Maternal and Infant Viral Resistance to the Maternal and Infant ARV Strategies

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since viral resistance was not a focus of the study.

    Time frame: Measured at the end of the 5-year study period

  14. Antepartum Component: Adherence to the Maternal Antiretroviral (ARV) Regimen, as Measured by Maternal Report

    The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since adherence was not a focus of the study.

    Time frame: Measured through the Week 1 postpartum study visit

07

Results

Posted Feb 9, 2018

Participant flow

From April 2011 to October 2014, pregnant or just-delivered women were recruited at medical centers in low-income countries.

Protocol Version 2.0: 04/2011-09/2012
Participant flow — Protocol Version 2.0: 04/2011-09/2012
MilestoneAntepartum Arm AAntepartum Arm BAntepartum Arm CLate Presenters
Started85586125129
Mothers that met all inclusion criteria85386124129
Completed62362016101
Not completed232241928
Withdrew: Protocol violation2001
Withdrew: Death6912
Withdrew: Withdrawal by subject8982210
Withdrew: Lost to follow-up7365210
Withdrew: Site closure151910
Withdrew: Subject unable to get to clinic446125
Withdrew: Other reason3510
Protocol Version 3.0: 10/2012-10/2014
Participant flow — Protocol Version 3.0: 10/2012-10/2014
MilestoneAntepartum Arm AAntepartum Arm BAntepartum Arm CLate Presenters
Started69468642275
Mothers that met all inclusion criteria69468442175
Completed54254834555
Not completed1521387720
Withdrew: Protocol violation0024
Withdrew: Adverse event1000
Withdrew: Death3511
Withdrew: Withdrawal by subject5452313
Withdrew: Lost to follow-up4936254
Withdrew: Site closure121120
Withdrew: Subject unable to get to clinic2826155
Withdrew: Other reason5813

Outcome measures

PrimaryAntepartum Component: Number of Confirmed Infant HIV Infections

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

Time frame:
Measured at birth or Week 1 study visit
Reported as:
Count of participants · Participants
Antepartum Component: Number of Confirmed Infant HIV Infections
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Antepartum Component: Number of Confirmed Infant HIV Infections2572
Statistical analysis
  • Antepartum Arm A vs Antepartum Arm B vs Antepartum Arm C · Risk difference (rd): -1.3 · 96.5% CI -2.1 to -0.4The combination of Arm B and Arm C minus Arm A, based on a repeated confidence interval (Lan-DeMets approach with an O'Brien-Fleming type I error spending function to preserve an experiment-wise type I error rate of 5%).
PrimaryAntepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events

These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

Time frame:
Measured through the Week 1 postpartum study visit
Reported as:
Count of participants · Participants
Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Periods 1 and 2261318—
Period 2596160
Statistical analysis
  • Antepartum Arm A vs Antepartum Arm B · Fisher Exact · p = 0.008
  • Antepartum Arm A vs Antepartum Arm C · Fisher Exact · p = 0.77
  • Antepartum Arm B vs Antepartum Arm C · Fisher Exact · p = >0.99
PrimaryAntepartum Component: Number of Mothers With Obstetrical Complications

Complications included deaths, diagnoses, signs/symptoms, chemistry lab tests, or hematological lab tests, with grades of 3 (Severe) or worse. Obstetrical complications were those classified by the MedDra coding system as "Pregnancy, puerperium and perinatal conditions", except if the condition was the death of the fetus: "Abortions not specified as induced or spontaneous", "Abortions spontaneous", or "Stillbirth and foetal death."

Time frame:
Measured through the Week 1 postpartum study visit
Reported as:
Count of participants · Participants
Antepartum Component: Number of Mothers With Obstetrical Complications
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Periods 1 and 28975—
Period 2201223
Statistical analysis
  • Antepartum Arm A vs Antepartum Arm B · Fisher Exact · p = 0.30
  • Antepartum Arm A vs Antepartum Arm C · Fisher Exact · p = 0.64
  • Antepartum Arm B vs Antepartum Arm C · Fisher Exact · p = 0.06
PrimaryAntepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies)

Composite outcome

Time frame:
Measured at birth
Reported as:
Count of participants · Participants
Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies)
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Periods 1 and 2389563—
Period 291123111
Statistical analysis
  • Antepartum Arm A vs Antepartum Arm B · Fisher Exact · p = <0.001
  • Antepartum Arm A vs Antepartum Arm C · Fisher Exact · p = 0.04
  • Antepartum Arm B vs Antepartum Arm C · Fisher Exact · p = 0.46
PrimaryPostpartum Component: Incidence of Confirmed Infant HIV Infection

Defined as infant 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. Analyses were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.

Time frame:
Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Reported as:
Number · New cases per 100 person-years
Postpartum Component: Incidence of Confirmed Infant HIV Infection
New cases per 100 person-yearsPostpartum Arm A (Maternal Prophylaxis)Postpartum Arm B (Infant Prophylaxis)
Postpartum Component: Incidence of Confirmed Infant HIV Infection0.560.55
Statistical analysis
  • Postpartum Arm A (Maternal Prophylaxis) vs Postpartum Arm B (Infant Prophylaxis) · Hazard ratio (hr): 1.0 · 96% CI 0.3 to 3.1The confidence interval was based on a repeated confidence interval.
PrimaryPostpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events

These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

Time frame:
Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Reported as:
Number · New cases per 100 person-years
Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
New cases per 100 person-yearsPostpartum Arm A (Maternal Prophylaxis)Postpartum Arm B (Infant Prophylaxis)
Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events14.414.1
Statistical analysis
  • Postpartum Arm A (Maternal Prophylaxis) vs Postpartum Arm B (Infant Prophylaxis) · Log Rank · p = 0.98
PrimaryMaternal Health Component: Incidence of Progression to AIDS-defining Illness or Death

AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses in Appendix IV of the protocol. These events were reviewed and confirmed by an Endpoint review group.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death0.240.49
Statistical analysis
  • Maternal Health Arm A (Continue Triple ARVs) vs Maternal Health Arm B (Discontinue Triple ARVs) · Log Rank · p = 0.37 · Hazard ratio (hr): 0.55 · 95% CI 0.14 to 2.08The hazard ratio compares Arm A relative to Arm B.
SecondaryAntepartum Component: Number of Infant HIV Infections

Detected by HIV NAT positivity

Time frame:
Measured at the birth (<= 3 days postpartum) visit
Reported as:
Count of participants · Participants
Antepartum Component: Number of Infant HIV Infections
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Antepartum Component: Number of Infant HIV Infections2242
SecondaryAntepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component)

For overall survival, failure was defined to be death. For HIV-free survival, failure was defined to be either death or developing HIV. The probability of living, or living without HIV infection, at 104 weeks was calculated by Kaplan-Meier estimation of the survival function.

Time frame:
Measured from birth through 104 weeks of age
Reported as:
Number · Proportional probability
Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component)
Proportional probabilityAntepartum Arm AAntepartum Arm BAntepartum Arm C
Overall survival, Periods 1 & 2 group (arms A & B only)0.959 (0.948 to 0.969)0.967 (0.955 to 0.975)—
Overall survival, period 2 group0.951 (0.920 to 0.970)0.982 (0.962 to 0.991)0.942 (0.914 to 0.962)
HIV-free survival, Periods 1&2 group (arms A&B only)0.937 (0.923 to 0.948)0.947 (0.933 to 0.958)—
HIV-free survival, period 2 group0.936 (0.903 to 0.958)0.940 (0.864 to 0.975)0.921 (0.887 to 0.946)
Statistical analysis
  • Antepartum Arm A vs Antepartum Arm B · Two-sided Z test · p = 0.16
  • Antepartum Arm A vs Antepartum Arm B · Two-sided Z test · p = 0.0156
  • Antepartum Arm A vs Antepartum Arm C · Two-sided Z test · p = 0.31
  • Antepartum Arm B vs Antepartum Arm C · Two-sided Z test · p = 0.0022
  • Antepartum Arm A vs Antepartum Arm B · Two-sided Z test · p = 0.13
  • Antepartum Arm A vs Antepartum Arm B · Two-sided Z test · p = 0.44
  • Antepartum Arm A vs Antepartum Arm C · Two-sided Z test · p = 0.24
  • Antepartum Arm B vs Antepartum Arm C · Two-sided Z test · p = 0.26
SecondaryAntepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery

Analysis used the principle of intent to treat.

Time frame:
Measured at the time of delivery
Reported as:
Count of participants · Participants
Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
ParticipantsAntepartum Arm AAntepartum Arm BAntepartum Arm C
Periods 1 and 2 — HIV RNA < 400 copies/mL4151092—
Periods 1 and 2 — HIV RNA >= 400 copies/mL929275—
Period 2 — HIV RNA < 400 copies/mL102259225
Period 2 — HIV RNA >= 400 copies/mL2106279
SecondaryPostpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery

Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit, confirmed by HIV NAT positivity of a second specimen drawn at a different time point, or infant death. Analyses (Kaplan-Meier probabilities) were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.

Time frame:
Measured through 24 months post-delivery
Reported as:
Number · Probability
Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery
ProbabilityPostpartum Arm A (Maternal Prophylaxis)Postpartum Arm B (Infant Prophylaxis)
Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery0.971 (0.959 to 0.980)0.977 (0.966 to 0.985)
SecondaryPostpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery

Analyses (Kaplan-Meier probabilities) conducted for all individual infants (rather than M-I pair)

Time frame:
Measured at 12 and 24 months post-delivery
Reported as:
Number · Probability
Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery
ProbabilityPostpartum Arm A (Maternal Prophylaxis)Postpartum Arm B (Infant Prophylaxis)
12 months post delivery0.988 (0.980 to 0.993)0.989 (0.981 to 0.994)
24 months post delivery0.978 (0.967 to 0.986)0.987 (0.979 to 0.992)
SecondaryMaternal Health Component: Incidence of Death

Number of women who died during the maternal health component; that is, who had been randomized to either continue or discontinue ART after risk of HIV vertical transmission through breastfeeding was over.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of Death
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of Death0.24 (0.18 to 0.32)0.43 (0.36 to 0.52)
SecondaryMaternal Health Component: Incidence of AIDS-defining Illness

"AIDS-defining illness" refers to the WHO Clinical Stage 4 illnesses listed in Appendix IV. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of AIDS-defining Illness
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of AIDS-defining Illness0.08 (0.05 to 0.12)0.25 (0.20 to 0.30)
SecondaryMaternal Health Component: Incidence of HIV/AIDS-related Events

"HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of HIV/AIDS-related Events
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of HIV/AIDS-related Events1.14 (0.89 to 1.45)1.24 (1.02 to 1.52)
SecondaryMaternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events

Cardiovascular or metabolic events of particular concern were included in this analysis. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Metabolic events considered were diabetes mellitus, lipodystrophy, or dyslipidemia. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · events per 100 person-years
Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events
events per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events2.9 (2.3 to 3.8)5.7 (4.8 to 6.7)
SecondaryMaternal Health Component: Other Targeted Medical Conditions

Other (non-cardiologic) medical conditions of particular concern were included in this outcome. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Events included were metabolic events, hepatic events, renal events, infections such as pulmonary tuberculosis, malaria, or other serious bacterial infections, and others.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · events per 100 person-years
Maternal Health Component: Other Targeted Medical Conditions
events per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Other Targeted Medical Conditions4.0 (3.2 to 4.9)4.6 (3.9 to 5.5)
SecondaryMaternal Health Component: Incidence of HIV/AIDS-related Event or Death

"HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of HIV/AIDS-related Event or Death
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of HIV/AIDS-related Event or Death1.30 (1.03 to 1.65)1.43 (1.17 to 1.74)
SecondaryMaternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events

"HIV/AIDS-related event" refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events3.47 (2.80 to 4.31)5.61 (4.83 to 6.53)
SecondaryMaternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern

Particular events were targeted as those of particular concern. This outcome considered all such events: death, events defining WHO stages II, III, or IV, targeted cardiovascular adverse events, other targeted adverse events, or cancers which were not AIDS-defining. A complete list can be found in Appendix IV of the Protocol. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · events per 100 person-years
Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern
events per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern9.0 (7.3 to 10.9)14.0 (12.1 to 16.1)
SecondaryMaternal Health Component: Incidence of Tuberculosis

Incidence of tuberculosis.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Incidence of Tuberculosis
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence of Tuberculosis0.40 (0.32 to 0.51)0.31 (0.24 to 0.39)
SecondaryMaternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results

The maternal safety endpoints summarized include grade 2, 3 or 4 hematologies (hemoglobin (Hb), White Blood Cells (WBC), Absolute Neutrophil Count (ANC), platelet count), chemistries (Alanine Aminotransferase (ALT or SGPT), serum creatinine), and grade 3 or 4 signs and symptoms that occurred post-randomization. These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · New cases per 100 person-years
Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results
New cases per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results15.3 (12.8 to 18.1)13.9 (11.9 to 16.3)
SecondaryMaternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event

This outcome included AIDS-defining illnesses or cardiovascular, hepatic, or renal adverse events of particular concern which were evaluated as serious. Serious outcomes were both those defined as serious according to the International Conference on Harmonization (ICH) definition, or outcomes with grades equal to or worse than 3 ("Severe"). A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy. Hepatic events considered were cirrhosis and idiopathic sclerosing cholangitis. Renal events considered were renal insufficiency, acute or chronic.

Time frame:
From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Reported as:
Number · events per 100 person-years
Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event
events per 100 person-yearsMaternal Health Arm A (Continue Triple ARVs)Maternal Health Arm B (Discontinue Triple ARVs)
Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event0.5 (0.4 to 0.6)0.9 (0.7 to 1.0)
Other pre-specifiedMaternal Health Component: Cost-effectiveness

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.

Time frame:
From study entry until July 7, 2015.

Results for this outcome have not been posted.

Other pre-specifiedMaternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since inflammation and thrombogenic markers were not a focus of the study.

Time frame:
From study entry until July 7, 2015.

Results for this outcome have not been posted.

Other pre-specifiedMaternal Health Component: Quality of Life

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since quality of life was not a focus of the study.

Time frame:
From study entry until July 7, 2015.

Results for this outcome have not been posted.

Other pre-specifiedMaternal Health Component: Self-reported Adherence

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.

Time frame:
From study entry until July 7, 2015.

Results for this outcome have not been posted.

Other pre-specifiedMaternal Health Component: Viral Resistance

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.

Time frame:
From study entry until July 7, 2015.

Results for this outcome have not been posted.

Other pre-specifiedPostpartum 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

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since functional maternal antibody and HIV-envelope binding responses were not a focus of the study.

Time frame:
Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first

Results for this outcome have not been posted.

Other pre-specifiedPostpartum 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

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since pharmacokinetics was not a focus of the study.

Time frame:
Measured through the last study visit during breastfeeding, or 18 months postpartum, whichever comes first

Results for this outcome have not been posted.

Other pre-specifiedPostpartum Component: Cost-effectiveness and Feasibility of the Study ARV Prophylaxis Regimens

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.

Time frame:
Measured at the end of the 5-year study period

Results for this outcome have not been posted.

Other pre-specifiedPostpartum Component: Rates and Patterns of Maternal and Infant Resistance to the Maternal and Infant ARV Regimens

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.

Time frame:
Measured at the end of the 5-year study period

Results for this outcome have not been posted.

Other pre-specifiedPostpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures

Adherence is by maternal report; adherence through hair analysis is not included here. The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.

Time frame:
Week 6 visit (14 days - 9 weeks postpartum); Week 14 visit (10-19 weeks postpartum); Week 26 visit (20 to 31 weeks postpartum); Week 50 visit (44 to 55 weeks postpartum); and Week 74 visit (68 to 80 weeks postpartum).
Reported as:
Count of participants · Participants
Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures
ParticipantsPostpartum Arm A (Maternal Prophylaxis)Postpartum Arm B (Infant Prophylaxis)
Week 6 visit — Never missed a dose10031104
Week 6 visit — Missed dose over 1 month ago120
Week 6 visit — Missed dose 2-4 weeks ago174
Week 6 visit — Missed dose within last 2 weeks14074
Week 14 visit — Never missed a dose9561081
Week 14 visit — Missed dose over 1 month ago200
Week 14 visit — Missed dose 2-4 weeks ago359
Week 14 visit — Missed dose within last 2 weeks11250
Week 26 visit — Never missed a dose8881035
Week 26 visit — Missed dose over 1 month ago481
Week 26 visit — Missed dose 2-4 weeks ago318
Week 26 visit — Missed dose within last 2 weeks10347
Week 50 visit — Never missed a dose716841
Week 50 visit — Missed dose over 1 month ago379
Week 50 visit — Missed dose 2-4 weeks ago347
Week 50 visit — Missed dose within last 2 weeks6430
Week 74 visit — Never missed a dose311377
Week 74 visit — Missed dose over 1 month ago152
Week 74 visit — Missed dose 2-4 weeks ago171
Week 74 visit — Missed dose within last 2 weeks349
Other pre-specifiedAntepartum 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

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since changes in HBV DNA Viral Load was not a focus of the study.

Time frame:
Measured at Week 8

Results for this outcome have not been posted.

Other pre-specifiedAntepartum Component: Cost Effectiveness and Feasibility of the Trial ARV Regimens

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since cost effectiveness was not a focus of the study.

Time frame:
Measured at the end of the 5-year study period

Results for this outcome have not been posted.

Other pre-specifiedAntepartum Component: Maternal and Infant Viral Resistance to the Maternal and Infant ARV Strategies

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since viral resistance was not a focus of the study.

Time frame:
Measured at the end of the 5-year study period

Results for this outcome have not been posted.

Other pre-specifiedAntepartum Component: Adherence to the Maternal Antiretroviral (ARV) Regimen, as Measured by Maternal Report

The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since adherence was not a focus of the study.

Time frame:
Measured through the Week 1 postpartum study visit

Results for this outcome have not been posted.

Adverse events

Collected over From study entry (for mothers) or birth (for infants) until study completion on September 30, 2016, an average of 169 weeks for mothers and through 24 months or September 30, 2016 for infants, whichever came first.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Mother, (AP) ZDV+sdNVP+TRV Tail9/1,547 (0.6%)267/1,547 (17.3%)1,413/1,547 (91.3%)
Mother, (AP) Triple ARV (3TC-ZDV/LPV-RTV)14/1,545 (0.9%)276/1,545 (17.9%)1,414/1,545 (91.5%)
Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV)2/445 (0.4%)69/445 (15.5%)388/445 (87.2%)
Mother, LP3/204 (1.5%)10/204 (4.9%)169/204 (82.8%)
Infant, (Mother Received ZDV+sdNVP+TRV Tail)59/1,500 (3.9%)296/1,500 (19.7%)1,406/1,500 (93.7%)
Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV))46/1,478 (3.1%)287/1,478 (19.4%)1,388/1,478 (93.9%)
Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV))27/429 (6.3%)113/429 (26.3%)403/429 (93.9%)
Infant, LP5/204 (2.5%)20/204 (9.8%)170/204 (83.3%)
Most frequent serious events
Showing 10 of 314
Most frequent serious events
EventMother, (AP) ZDV+sdNVP+TRV TailMother, (AP) Triple ARV (3TC-ZDV/LPV-RTV)Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV)Mother, LPInfant, (Mother Received ZDV+sdNVP+TRV Tail)Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV))Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV))Infant, LP
Premature babyPregnancy, puerperium and perinatal conditions0/15470/15450/4450/20425/150042/147819/4290/204
Sepsis neonatalInfections and infestations0/15470/15450/4450/20447/150033/147811/4293/204
PneumoniaInfections and infestations2/15475/15450/4450/20434/150033/14788/4296/204
MalnutritionMetabolism and nutrition disorders0/15470/15450/4450/20422/150020/147811/4292/204
Foetal deathPregnancy, puerperium and perinatal conditions25/154737/15457/4451/2040/15000/14780/4290/204
Neonatal asphyxiaRespiratory, thoracic and mediastinal disorders0/15470/15450/4450/20411/15004/147810/4290/204
GastroenteritisInfections and infestations5/154710/15451/4450/20429/150026/14788/4292/204
Premature labourPregnancy, puerperium and perinatal conditions16/154715/15458/4450/2040/15000/14780/4290/204
Pneumonia bacterialInfections and infestations3/15474/15450/4450/20423/150015/14785/4290/204
AnaemiaBlood and lymphatic system disorders13/154716/15454/4453/20410/150011/14780/4290/204
Most frequent other events
Showing 10 of 41
Most frequent other events
EventMother, (AP) ZDV+sdNVP+TRV TailMother, (AP) Triple ARV (3TC-ZDV/LPV-RTV)Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV)Mother, LPInfant, (Mother Received ZDV+sdNVP+TRV Tail)Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV))Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV))Infant, LP
Haemoglobin decreasedInvestigations764/1547791/1545191/445103/2041226/15001230/1478356/429124/204
Neutrophil count decreasedInvestigations668/1547619/1545161/44567/204859/1500848/1478255/429115/204
Alanine aminotransferase increasedInvestigations470/1547493/1545116/44536/204106/150066/147812/42914/204
DiarrhoeaGastrointestinal disorders179/1547202/154541/4455/204307/1500317/147852/42916/204
GastroenteritisInfections and infestations111/1547101/154525/44521/204227/1500205/147858/42938/204
CoughRespiratory, thoracic and mediastinal disorders179/1547173/154520/4456/204274/1500253/147835/42917/204
PregnancyPregnancy, puerperium and perinatal conditions272/1547271/154552/44526/2040/15000/14780/4290/204
PyrexiaGeneral disorders118/154792/154526/4454/204260/1500240/147848/42918/204
Vulvovaginal candidiasisInfections and infestations229/1547206/154568/44514/2042/15003/14780/4290/204
HeadacheNervous system disorders189/1547188/154523/4458/2040/15000/14780/4290/204

Baseline characteristics

All women in 1077BF/1077FF except those considered ineligible for the analysis after team review.

Age, Continuous
Age, Continuous(years)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Median26.5 (22.8 to 30.1)26.6 (23.3 to 30.3)26.4 (22.7 to 30.4)26.8 (23.2 to 31.1)26.5 (23.0 to 30.3)
Sex: Female, Male
Sex: Female, Male(Participants)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Female154715454452043741
Male00000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Black Non-Hispanic149314874401833603
Hispanic (Regardless of Race)7124225
Asian, Pacific Islander4746119113
Region of Enrollment
Region of Enrollment(Participants)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Malawi489493155311168
Tanzania232410057
South Africa51351078271128
Uganda207205859506
Zimbabwe23723699116688
Zambia323118283
India4646019111
Weight
Weight(kg)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Median64 (57.5 to 73.5)64.6 (58 to 74.1)64.4 (58 to 75.9)60.9 (53 to 68.9)64 (57.5 to 74)
BMI
BMI(kg/m^2)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Median25.9 (23.5 to 29.5)26.3 (23.4 to 29.8)26.3 (23.5 to 30.1)23.6 (21.8 to 26.8)26 (23.4 to 29.6)
HIV RNA level prior to randomization
HIV RNA level prior to randomization(copies/ml)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Median6409 (1450.5 to 22720)8002 (1854 to 28767)8393 (1909 to 28454)12140 (2407.5 to 39138.5)7409 (1708 to 26350)
Viral Load at enrollment
Viral Load at enrollment(log10 copies/mL)Antepartum Arm AAntepartum Arm BAntepartum Arm CLate PresentersTotal
Median3.8 (3.2 to 4.4)3.9 (3.3 to 4.5)3.9 (3.3 to 4.5)4.1 (3.4 to 4.6)3.9 (3.2 to 4.4)

13 further baseline measures are reported on the registry.

08

Study locations

14 sites
  • Byramjee Jeejeebhoy Medical College (BJMC) CRS
    Pune, Maharashtra 411001, India
  • Blantyre CRS
    Blantyre, Malawi
  • Malawi CRS
    Lilongwe, Malawi
  • Soweto IMPAACT CRS
    Johannesburg, Gauteng 1862, South Africa
  • Shandukani Research CRS
    Johannesburg, Gauteng 2001, South Africa
  • Durban Paediatric HIV CRS
    Durban, KwaZulu-Natal 4001, South Africa
  • Umlazi CRS
    Durban, KwaZulu-Natal 4001, South Africa
  • Family Clinical Research Unit (FAM-CRU) CRS
    Cape Town, Western Cape 7505, South Africa
  • Kilimanjaro Christian Medical Centre (KCMC)
    Moshi, Tanzania
  • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
    Kampala, Uganda
  • George CRS
    Lusaka, Zambia
  • Seke North CRS
    Chitungwiza, Zimbabwe
  • St Mary's CRS
    Chitungwiza, Zimbabwe
  • Harare Family Care CRS
    Harare, Zimbabwe
09

References and documents

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 Jun;29(6):514-8. doi: 10.1097/INF.0b013e3181cda531. PubMed 20054287 ↗
  • 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. doi: 10.1086/648446. PubMed 19916796 ↗
  • U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0. [Updated August 2009]. Available from: http://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
  • WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-related Disease in Adults and Children, World Health Organization, 2007. Available: http://apps.who.int/iris/handle/10665/43699
  • Bhattacharya D, Tierney C, Butler K, Kiweewa FM, Moodley D, Govender V, Vhembo T, Mohtashemi N, Ship H, Dula D, George K, Chaktoura N, Fowler MG, Peters MG, Currier JS. Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial. Obstet Gynecol. 2023 Sep 1;142(3):613-624. doi: 10.1097/AOG.0000000000005302. Epub 2023 Aug 3. PubMed 37535953 ↗
  • Vhembo T, Baltrusaitis K, Tierney C, Owor M, Dadabhai S, Violari A, Theron G, Moodley D, Mukwasi-Kahari C, George K, Shepherd J, Siberry GK, Browning R, Fowler MG, Stranix-Chibanda L; IMPAACT P1084s study team. Bone and Renal Health in Infants With or Without Breastmilk Exposure to Tenofovir-Based Maternal Antiretroviral Treatment in the PROMISE Randomized Trial. J Acquir Immune Defic Syndr. 2023 Aug 15;93(5):431-437. doi: 10.1097/QAI.0000000000003218. PubMed 37199427 ↗
  • Nevrekar N, Butler K, Shapiro DE, Atuhaire P, Taha TE, Makanani B, Chinula L, Owor M, Moodley D, Chipato T, McCarthy K, Flynn PM, Currier J, Fowler MG, Gupta A, Suryavanshi N. Self-reported Antiretroviral Adherence: Association With Maternal Viral Load Suppression in Postpartum Women Living With HIV-1 From Promoting Maternal and Infant Survival Everywhere, a Randomized Controlled Trial in Sub-Saharan Africa and India. J Acquir Immune Defic Syndr. 2023 Jan 1;92(1):76-83. doi: 10.1097/QAI.0000000000003102. Epub 2022 Sep 28. PubMed 36170749 ↗
  • Baltrusaitis K, Makanani B, Tierney C, Fowler MG, Moodley D, Theron G, Nyakudya LH, Tomu M, Fairlie L, George K, Heckman B, Knowles K, Browning R, Siberry GK, Taha TE, Stranix-Chibanda L; PROMISE P1084s Study Team. Maternal and infant renal safety following tenofovir disoproxil fumarate exposure during pregnancy in a randomized control trial. BMC Infect Dis. 2022 Jul 20;22(1):634. doi: 10.1186/s12879-022-07608-8. PubMed 35858874 ↗
  • Fowler MG, Aizire J, Sikorskii A, Atuhaire P, Ogwang LW, Mutebe A, Katumbi C, Maliwichi L, Familiar I, Taha T, Boivin MJ; PROMISE-NEURODEV study team. Growth deficits in antiretroviral and HIV-exposed uninfected versus unexposed children in Malawi and Uganda persist through 60 months of age. AIDS. 2022 Mar 15;36(4):573-582. doi: 10.1097/QAD.0000000000003122. PubMed 34750297 ↗
  • Stranix-Chibanda L, Tierney C, Pinilla M, George K, Aizire J, Chipoka G, Mallewa M, Naidoo M, Nematadzira T, Kusakara B, Violari A, Mbengeranwa T, Njau B, Fairlie L, Theron G, Mubiana-Mbewe M, Khadse S, Browning R, Fowler MG, Siberry GK; PROMISE Study Team. Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial. PLoS One. 2021 Aug 20;16(8):e0255250. doi: 10.1371/journal.pone.0255250. eCollection 2021. PubMed 34415933 ↗
  • Theron G, Brummel S, Fairlie L, Pinilla M, McCarthy K, Owor M, Chinula L, Makanani B, Violari A, Moodley D, Chakhtoura N, Browning R, Hoffman R, Fowler MG. Pregnancy Outcomes of Women Conceiving on Antiretroviral Therapy (ART) Compared to Those Commenced on ART During Pregnancy. Clin Infect Dis. 2021 Jul 15;73(2):e312-e320. doi: 10.1093/cid/ciaa805. PubMed 32564058 ↗
  • Aizire J, Sikorskii A, Ogwang LW, Kawalazira R, Mutebe A, Familiar-Lopez I, Mallewa M, Taha T, Boivin MJ, Fowler MG; PROMISE-NEURODEV study team. Decreased growth among antiretroviral drug and HIV-exposed uninfected versus unexposed children in Malawi and Uganda. AIDS. 2020 Feb 1;34(2):215-225. doi: 10.1097/QAD.0000000000002405. PubMed 31634154 ↗
  • Hoffman RM, Angelidou KN, Brummel SS, Saidi F, Violari A, Dula D, Mave V, Fairlie L, Theron G, Kamateeka M, Chipato T, Chi BH, Stranix-Chibanda L, Nematadzira T, Moodley D, Bhattacharya D, Gupta A, Coletti A, McIntyre JA, Klingman KL, Chakhtoura N, Shapiro DE, Fowler MG, Currier JS; IMPAACT PROMISE 1077BF/FF team. Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial. HIV Clin Trials. 2018 Dec;19(6):209-224. doi: 10.1080/15284336.2018.1537327. PubMed 30890061 ↗
  • Fowler MG, Qin M, Fiscus SA, Currier JS, Flynn PM, Chipato T, McIntyre J, Gnanashanmugam D, Siberry GK, Coletti AS, Taha TE, Klingman KL, Martinson FE, Owor M, Violari A, Moodley D, Theron GB, Bhosale R, Bobat R, Chi BH, Strehlau R, Mlay P, Loftis AJ, Browning R, Fenton T, Purdue L, Basar M, Shapiro DE, Mofenson LM; IMPAACT 1077BF/1077FF PROMISE Study Team. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention. N Engl J Med. 2016 Nov 3;375(18):1726-1737. doi: 10.1056/NEJMoa1511691. PubMed 27806243 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 11, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01061151
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Feb 2, 2010
Start date
Mar 1, 2011
Primary completion
Sep 30, 2016
Completion
Sep 30, 2016
Results posted
Feb 9, 2018
Last update
Feb 11, 2022

Study contacts

Mary Glenn Fowler, MD, MPH
study chair · Johns Hopkins Medical Institute, Makerere U.-JHU Research Collaboration

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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