Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries
PROMISE
Breastfeeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)
3 other identifiers
interventional
3,747
6 countries
13
Brief 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)?
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hiv-infections
Started Mar 2011
Longer than P75 for phase_3 hiv-infections
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2010
CompletedFirst Posted
Study publicly available on registry
February 2, 2010
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2016
CompletedResults Posted
Study results publicly available
February 9, 2018
CompletedFebruary 11, 2022
February 1, 2022
5.6 years
February 1, 2010
September 28, 2017
February 9, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
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 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 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 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 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 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 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.
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
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)
Measured from birth through 104 weeks of age
Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
Measured at the time of delivery
Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery
Measured through 24 months post-delivery
Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery
Measured at 12 and 24 months post-delivery
- +11 more secondary outcomes
Other Outcomes (14)
Maternal Health Component: Cost-effectiveness
From study entry until July 7, 2015.
Maternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers
From study entry until July 7, 2015.
Maternal Health Component: Quality of Life
From study entry until July 7, 2015.
- +11 more other outcomes
Study Arms (8)
Antepartum Arm A
ACTIVE COMPARATORMothers received ZDV + sdNVP + TRV Tail
Antepartum Arm B
EXPERIMENTALMothers received Triple ARV (3TC-ZDV + LPV-RTV)
Antepartum Arm C
EXPERIMENTALMothers received Triple ARV (TRV + LPV-RTV)
Late Presenters
OTHERRegistration to facilitate a structure to screen women and infants for randomization in the Postpartum Component.
Postpartum Arm A (Maternal Prophylaxis)
EXPERIMENTALMothers received prophylaxis \[preferred regimen: TRV + LPV-RTV\]. Infants received short-course NVP.
Postpartum Arm B (Infant Prophylaxis)
EXPERIMENTALInfants received extended NVP.
Maternal Health Arm A (Continue triple ARVs)
EXPERIMENTALMothers continued receiving triple ARV regimen \[preferred regimen: TRV + LPV-RTV\].
Maternal Health Arm B (Discontinue triple ARVs)
ACTIVE COMPARATORMothers discontinued triple ARV regimen.
Interventions
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.
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.
200 mg/300 mg
Oral suspension (dosing according to birth weight) once a day through 42 days of age or through the week 6 visit, whichever is later.
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.
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.
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).
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).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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)
- 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
- 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)
- +54 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
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
Related Publications (14)
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.
PMID: 20054287BACKGROUNDBecquet 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.
PMID: 19916796BACKGROUNDU.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
RESULTWHO 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
RESULTBhattacharya 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.
PMID: 37535953DERIVEDVhembo 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.
PMID: 37199427DERIVEDNevrekar 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.
PMID: 36170749DERIVEDBaltrusaitis 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.
PMID: 35858874DERIVEDFowler 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.
PMID: 34750297DERIVEDStranix-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.
PMID: 34415933DERIVEDTheron 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.
PMID: 32564058DERIVEDAizire 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.
PMID: 31634154DERIVEDHoffman 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.
PMID: 30890061DERIVEDFowler 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.
PMID: 27806243DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- IMPAACT Clinicaltrials.gov Coordinator
- Organization
- Family Health International (FHI 360)
Study Officials
- STUDY CHAIR
Mary Glenn Fowler, MD, MPH
Johns Hopkins Medical Institute, Makerere U.-JHU Research Collaboration
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The investigators and outcomes assessor did not receive by-arm tabulations while the study was ongoing.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2010
First Posted
February 2, 2010
Study Start
March 1, 2011
Primary Completion
September 30, 2016
Study Completion
September 30, 2016
Last Updated
February 11, 2022
Results First Posted
February 9, 2018
Record last verified: 2022-02