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

Summary

The purpose of this study was to examine, in an integrated and comprehensive fashion, three critical questions currently facing HIV-infected pregnant and postpartum women and their infants: 1. What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV? 2. What is the optimal intervention for the prevention of postpartum transmission in breastfeeding (BF) infants? 3. What is the optimal intervention for the preservation of maternal health after the risk period for prevention of mother-to-child-transmission ends (either at delivery or cessation of BF)? The overall PROMISE protocol had three separate interventional components to address each of these three questions and was conducted at locations in Africa and other parts of the world. Due to variations in the standard of care for HIV-infected pregnant and postpartum women and their infants at different sites, not all of these questions were relevant. Therefore, two separate versions of the PROMISE protocol were developed, each containing only the relevant components. The 1077BF protocol was used at sites where the standard method of infant feeding was breastfeeding, whereas the 1077FF protocol was used at sites where the standard method of infant feeding was formula feeding. The analyses were collapsed across the two protocol versions, and therefore the summaries contain the results of the 1077BF and/or the 1077FF protocols.

Timeline

Start

2011-03-01

Primary completion

2016-09-30

Completion

2016-09-30

Outcome

Mixed primary results

paper The rate of transmission was significantly lower with ART than with zidovudine alone PMID 27806243 ↗

paper the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008) PMID 27806243 ↗

Publications

• Background 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.
• Background 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.
• Results 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
• Results 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Emtricitabine-tenofovir disoproxil fumarate	Unknown	200 mg	Oral
Comparator	Emtricitabine-tenofovir disoproxil fumarate	Unknown	300 mg	Oral
Subject	Lamivudine-Zidovudine	Unknown	150 mg	—
Subject	Lamivudine-Zidovudine	Unknown	300 mg	—
Comparator	Nevirapine	Small molecule	200 mg	Oral
Comparator	Zidovudine	Small molecule	300 mg	—
Subject	lopinavir-ritonavir	Unknown	100 mg	—
Subject	lopinavir-ritonavir	Unknown	150 mg	—
Subject	lopinavir-ritonavir	Unknown	400 mg	—
Subject	lopinavir-ritonavir	Unknown	600 mg	—

Indications