HIV InfectionsPhase 3PROMISENCT01061151

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

A Phase 3 study testing Zidovudine (ZDV), Nevirapine (NVP): Antepartum Mothers and Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age
Conditions the study is for: HIV Infections
What is being tested?: Zidovudine (ZDV), Nevirapine (NVP): Antepartum Mothers and Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3,747 participants
Where: 14 sitesin 7 countries
Study dates: 1 Mar 2011to 30 Sep 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

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:

Hemoglobin greater than or equal to 7.5 g/dL
White blood cell count (WBC) greater than or equal to 1,500 cells/mm^3
Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
Platelets greater than or equal to 50,000 cells/mm^3
Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN)
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:

Hemoglobin greater than or equal to 7.0 g/dL
WBC greater than or equal to 1,500 cells/mm^3
ANC greater than or equal to 750 cells/mm^3
Platelets greater than or equal to 50,000 cells/mm^3
ALT less than or equal to 2.5 times the upper limit of normal (ULN)
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):

Hemoglobin greater than or equal to 10 g/dL
WBC greater than or equal to 1,500 cells/mm^3
ANC greater than or equal to 750 cells/mm^3
Platelets greater than or equal to 50,000 cells/mm^3
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:

ANC greater than or equal to 750 cells/mm^3
Hemoglobin greater than or equal to 7.0 gm/dL
Platelet count greater than or equal to 50,000 cells/mm^3
ALT (SGPT) less than or equal to 2.5 times the ULN
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

Trial locations and contacts

14 sites in 7 countries.

Country

City, postcode or hospital

14 sites in 7 countries

South Africa5 sites

Family Clinical Research Unit (FAM-CRU) CRS
Cape Town, Western Cape, 7505
Durban Paediatric HIV CRS
Durban, KwaZulu-Natal, 4001
Umlazi CRS
Durban, KwaZulu-Natal, 4001
Soweto IMPAACT CRS
Johannesburg, Gauteng, 1862
Shandukani Research CRS
Johannesburg, Gauteng, 2001

Other trials in South Africa

Zimbabwe3 sites

Seke North CRS
Chitungwiza
St Mary's CRS
Chitungwiza
Harare Family Care CRS
Harare

Other trials in Zimbabwe

Malawi2 sites

Blantyre CRS
Blantyre
Malawi CRS
Lilongwe

Other trials in Malawi

India1 site

Byramjee Jeejeebhoy Medical College (BJMC) CRS
Pune, Maharashtra, 411001

Other trials in India

Tanzania1 site

Kilimanjaro Christian Medical Centre (KCMC)
Moshi

Other trials in Tanzania

Uganda1 site

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
Kampala

Other trials in Uganda

Zambia1 site

George CRS
Lusaka

Other trials in Zambia

About this study

Official title: Breastfeeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)

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:

What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV?
What is the optimal intervention for the prevention of postpartum transmission in breastfeeding (BF) infants?
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:

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.

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.

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.

Conditions: HIV Infections
Being tested: Zidovudine (ZDV), Nevirapine (NVP): Antepartum Mothers, Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail, Lamivudine-Zidovudine (3TC-ZDV), Lopinavir-ritonavir (LPV-RTV)
Keywords: Mother to Child Transmission, HIV Infection, HAART, Maternal Health, Breastfeeding, Perinatal transmission
Medical subject headings: HIV Infections, Breast Feeding

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Zidovudine (ZDV)Drug
300 mg twice daily
Nevirapine (NVP): Antepartum MothersDrug
200 mg at onset of labor
Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tailDrug
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.
Lamivudine-Zidovudine (3TC-ZDV)Drug
150 mg/300 mg twice daily
Lopinavir-ritonavir (LPV-RTV)Drug
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.
Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])Drug
200 mg/300 mg
Nevirapine (NVP): Infant short-courseDrug
Oral suspension (dosing according to birth weight) once a day through 42 days of age or through the week 6 visit, whichever is later.
Nevirapine (NVP): Infant extendedDrug
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.
No InterventionOther
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.
Discontinue triple ARVsOther
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).
Continue triple ARVsOther
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).

Study groups in NCT01061151
Study group	Role	What they receive
Antepartum Arm A	Active comparator	Mothers received ZDV + sdNVP + TRV Tail Receives: Drug: Zidovudine (ZDV); Drug: Nevirapine (NVP): Antepartum Mothers; Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail; Drug: Nevirapine (NVP): Infant short-course
Antepartum Arm B	Experimental	Mothers received Triple ARV (3TC-ZDV + LPV-RTV) Receives: Drug: Lamivudine-Zidovudine (3TC-ZDV); Drug: Lopinavir-ritonavir (LPV-RTV); Drug: Nevirapine (NVP): Infant short-course
Antepartum Arm C	Experimental	Mothers received Triple ARV (TRV + LPV-RTV) Receives: Drug: Lopinavir-ritonavir (LPV-RTV); Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]); Drug: Nevirapine (NVP): Infant short-course
Late Presenters	Other	Registration to facilitate a structure to screen women and infants for randomization in the Postpartum Component. Receives: Other: No Intervention
Postpartum Arm A (Maternal Prophylaxis)	Experimental	Mothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP. Receives: Drug: Lopinavir-ritonavir (LPV-RTV); Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]); Drug: Nevirapine (NVP): Infant short-course
Postpartum Arm B (Infant Prophylaxis)	Experimental	Infants received extended NVP. Receives: Drug: Nevirapine (NVP): Infant extended
Maternal Health Arm A (Continue triple ARVs)	Experimental	Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV]. Receives: Other: Continue triple ARVs
Maternal Health Arm B (Discontinue triple ARVs)	Active comparator	Mothers discontinued triple ARV regimen. Receives: Other: Discontinue triple ARVs

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Measured at birth or Week 1 study visit
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).
Measured: Measured through the Week 1 postpartum study visit
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."
Measured: Measured through the Week 1 postpartum study visit
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
Measured: Measured at birth
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.
Measured: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
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).
Measured: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

Secondary outcomes (16)

Antepartum Component: Number of Infant HIV Infections
Detected by HIV NAT positivity
Measured: Measured at the birth (<= 3 days postpartum) visit
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.
Measured: Measured from birth through 104 weeks of age
Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
Analysis used the principle of intent to treat.
Measured: Measured at the time of delivery
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.
Measured: Measured through 24 months post-delivery
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)
Measured: Measured at 12 and 24 months post-delivery
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of Tuberculosis
Incidence of tuberculosis.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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).
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.
Measured: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 201130 Sep 2016

First posted2 Feb 2010 (estimated)
Study start1 Mar 2011
Primary completion30 Sep 2016
Study completion30 Sep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (14)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Investigator, Outcomes assessor
Enrolment: 3,747 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01061151
Sponsor's protocol ID: 1077BF (PROMISE)
Other IDs: 10777, IMPAACT 1077BF
Acronym: PROMISE
Status last verified: Feb 2022
First submitted: 1 Feb 2010
Last updated: 11 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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

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Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Breastfeeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)
ClinicalTrials.gov ID: NCT01061151
Acronym / sponsor ID: PROMISE / 1077BF (PROMISE)
Conditions: HIV Infections
Keywords: Mother to Child Transmission, HIV Infection, HAART, Maternal Health, Breastfeeding, Perinatal transmission
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,747 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 1 Mar 2011 (actual)
Primary completion: 30 Sep 2016 (actual)
Study completion: 30 Sep 2016 (actual)
First posted: 2 Feb 2010 (estimated)
Results: Posted 9 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV?
What is the optimal intervention for the prevention of postpartum transmission in breastfeeding (BF) infants?
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)?

Detailed description

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.

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.

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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (investigator, outcomes assessor)
Number of arms: 8

Arm	Type	Receives
Antepartum Arm A	Active comparator	Drug: Zidovudine (ZDV), Drug: Nevirapine (NVP): Antepartum Mothers, Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail, Drug: Nevirapine (NVP): Infant short-courseMothers received ZDV + sdNVP + TRV Tail
Antepartum Arm B	Experimental	Drug: Lamivudine-Zidovudine (3TC-ZDV), Drug: Lopinavir-ritonavir (LPV-RTV), Drug: Nevirapine (NVP): Infant short-courseMothers received Triple ARV (3TC-ZDV + LPV-RTV)
Antepartum Arm C	Experimental	Drug: Lopinavir-ritonavir (LPV-RTV), Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]), Drug: Nevirapine (NVP): Infant short-courseMothers received Triple ARV (TRV + LPV-RTV)
Late Presenters	Other	Other: No InterventionRegistration to facilitate a structure to screen women and infants for randomization in the Postpartum Component.
Postpartum Arm A (Maternal Prophylaxis)	Experimental	Drug: Lopinavir-ritonavir (LPV-RTV), Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]), Drug: Nevirapine (NVP): Infant short-courseMothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP.
Postpartum Arm B (Infant Prophylaxis)	Experimental	Drug: Nevirapine (NVP): Infant extendedInfants received extended NVP.
Maternal Health Arm A (Continue triple ARVs)	Experimental	Other: Continue triple ARVsMothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Maternal Health Arm B (Discontinue triple ARVs)	Active comparator	Other: Discontinue triple ARVsMothers discontinued triple ARV regimen.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Zidovudine (ZDV)300 mg twice daily	Drug	Antepartum Arm A
Nevirapine (NVP): Antepartum Mothers200 mg at onset of labor	Drug	Antepartum Arm A
Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail200 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.	Drug	Antepartum Arm A
Lamivudine-Zidovudine (3TC-ZDV)150 mg/300 mg twice daily	Drug	Antepartum Arm B
Lopinavir-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.	Drug	Antepartum Arm B, Antepartum Arm C, Postpartum Arm A (Maternal Prophylaxis)
Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])200 mg/300 mg	Drug	Antepartum Arm C, Postpartum Arm A (Maternal Prophylaxis)
Nevirapine (NVP): Infant short-courseOral suspension (dosing according to birth weight) once a day through 42 days of age or through the week 6 visit, whichever is later.	Drug	Antepartum Arm A, Antepartum Arm B, Antepartum Arm C, Postpartum Arm A (Maternal Prophylaxis)
Nevirapine (NVP): Infant extendedOral 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.	Drug	Postpartum Arm B (Infant Prophylaxis)
No InterventionWomen 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.	Other	Late Presenters
Discontinue triple ARVsARVs 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).	Other	Maternal Health Arm B (Discontinue triple ARVs)
Continue triple ARVsMothers 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).	Other	Maternal Health Arm A (Continue triple ARVs)

Primary outcome

Antepartum Component: Number of Confirmed Infant HIV Infections
Time frame: Measured at birth or Week 1 study visit
Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point
Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
Time frame: Measured through the Week 1 postpartum study visit
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).
Antepartum Component: Number of Mothers With Obstetrical Complications
Time frame: Measured through the Week 1 postpartum study visit
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."
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)
Time frame: Measured at birth
Composite outcome
Postpartum Component: Incidence of Confirmed Infant HIV Infection
Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
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.
Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
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).
Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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.

16 secondary outcomes

Antepartum Component: Number of Infant HIV Infections
Time frame: Measured at the birth (<= 3 days postpartum) visit
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)
Time frame: Measured from birth through 104 weeks of age
Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
Time frame: Measured at the time of delivery
Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery
Time frame: Measured through 24 months post-delivery
Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery
Time frame: Measured at 12 and 24 months post-delivery
Maternal Health Component: Incidence of Death
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of AIDS-defining Illness
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of HIV/AIDS-related Events
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Other Targeted Medical Conditions
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of HIV/AIDS-related Event or Death
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence of Tuberculosis
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
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
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.

Results and safety

Results posted to the registry on 9 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Antepartum Arm A	855	623
Antepartum Arm B	861	620
Antepartum Arm C	25	16
Late Presenters	129	101

Primary outcome: Antepartum Component: Number of Confirmed Infant HIV Infections

Time frame: Measured at birth or Week 1 study visit. Count of participants. Unit: Participants

Measure	Antepartum Arm A n = 1386	Antepartum Arm B n = 1385	Antepartum Arm C n = 325
Value	25	7	2

Antepartum Arm A vs Antepartum Arm B vs Antepartum Arm C: Risk Difference (RD): -1.3 (96.5% CI -2.1 to -0.4)

Population analysed: Analysis includes data from periods 1 and 2. Analysis is among the live births with HIV test results summarized for the maternal-infant set (the worst outcome summarized for cases of multiple births). Analysis used the principle of intent to treat.

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

Time frame: Measured through the Week 1 postpartum study visit. Count of participants. Unit: Participants

Measure	Antepartum Arm A n = 1521	Antepartum Arm B n = 1520	Antepartum Arm C n = 424
Periods 1 and 2	261	318	–
Period 2	59	61	60

Antepartum Arm A vs Antepartum Arm B: p = 0.008, Fisher Exact
Antepartum Arm A vs Antepartum Arm C: p = 0.77, Fisher Exact
Antepartum Arm B vs Antepartum Arm C: p >0.99, Fisher Exact

Population analysed: Mothers with no safety data available after baseline were not included. Analysis used the principle of intent to treat.

Primary outcome: Antepartum Component: Number of Mothers With Obstetrical Complications

Time frame: Measured through the Week 1 postpartum study visit. Count of participants. Unit: Participants

Measure	Antepartum Arm A n = 1521	Antepartum Arm B n = 1520	Antepartum Arm C n = 424
Periods 1 and 2	89	75	–
Period 2	20	12	23

Antepartum Arm A vs Antepartum Arm B: p = 0.30, Fisher Exact
Antepartum Arm A vs Antepartum Arm C: p = 0.64, Fisher Exact
Antepartum Arm B vs Antepartum Arm C: p = 0.06, Fisher Exact

Population analysed: Mothers who do not have any obstetrical complications information available after study entry are not included. Analysis used the principle of intent to treat.

Primary outcome: 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)

Time frame: Measured at birth. Count of participants. Unit: Participants

Measure	Antepartum Arm A n = 1451	Antepartum Arm B n = 1447	Antepartum Arm C n = 372
Periods 1 and 2	389	563	–
Period 2	91	123	111

Antepartum Arm A vs Antepartum Arm B: p <0.001, Fisher Exact
Antepartum Arm A vs Antepartum Arm C: p = 0.04, Fisher Exact
Antepartum Arm B vs Antepartum Arm C: p = 0.46, Fisher Exact

Population analysed: Includes mothers with confirmed infant birth outcome as live birth, stillbirth, or spontaneous abortion and outcome assessments. Multiple gestation pregnancies (twins and triplets) were summarized at the unique mother level. Analysis used the principle of intent to treat.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mother, (AP) ZDV+sdNVP+TRV Tail	267 of 1,547 (17.3%)	1,413 of 1,547 (91.3%)	9 of 1,547
Mother, (AP) Triple ARV (3TC-ZDV/LPV-RTV)	276 of 1,545 (17.9%)	1,414 of 1,545 (91.5%)	14 of 1,545
Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV)	69 of 445 (15.5%)	388 of 445 (87.2%)	2 of 445
Mother, LP	10 of 204 (4.9%)	169 of 204 (82.8%)	3 of 204
Infant, (Mother Received ZDV+sdNVP+TRV Tail)	296 of 1,500 (19.7%)	1,406 of 1,500 (93.7%)	59 of 1,500
Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV))	287 of 1,478 (19.4%)	1,388 of 1,478 (93.9%)	46 of 1,478
Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV))	113 of 429 (26.3%)	403 of 429 (93.9%)	27 of 429
Infant, LP	20 of 204 (9.8%)	170 of 204 (83.3%)	5 of 204

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20054287Taha 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.
Background: PubMed 19916796Becquet 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.
Results publicationU.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
Results publicationWHO 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
Derived from this study: PubMed 37535953Bhattacharya 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.
Derived from this study: PubMed 37199427Vhembo 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.
Derived from this study: PubMed 36170749Nevrekar 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.
Derived from this study: PubMed 35858874Baltrusaitis 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.
Derived from this study: PubMed 34750297Fowler 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.
Derived from this study: PubMed 34415933Stranix-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.
Derived from this study: PubMed 32564058Theron 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.
Derived from this study: PubMed 31634154Aizire 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.
IMPAACT Study 1077BFLink provided by the sponsor.
MedDra coding of complicationsLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mary Glenn Fowler, MD, MPH study chair

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

14 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in South Africa, Zimbabwe, Malawi, India, Tanzania and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Antepartum Component: Number of Confirmed Infant HIV Infections (time frame: Measured at birth or Week 1 study visit). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01061151, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2022.