Prevention of HIV-1 transmission through breastfeeding:efficacy of safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE)

Post Date: 
2018-04-01
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Publication: 
Journal of Acquired Immune Deficiency Syndromes
Summary: 

BACKGROUND:
No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child transmission throughout the breastfeeding period.

SETTING:
Fourteen sites in Sub-Saharan Africa and India.

METHODS:
A randomized, open-label strategy trial was conducted in HIV-1-infected women with CD4 counts ≥350 cells/mm (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1-uninfected newborns. Randomization at 6-14 days postpartum was to mART or infant nevirapine (iNVP) prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother-infant pairs except those with infant HIV-1 infection at entry.

RESULTS:
Between June 2011 and October 2014, 2431 mother-infant pairs were enrolled; 97% of women were World Health Organization Clinical Stage I, median screening CD4 count 686 cells/mm. Median infant gestational age/birth weight was 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and 7 of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio 1.0, 96% repeated confidence interval 0.3-3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening, or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively).

CONCLUSIONS:
Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1-free survival at 24 months.

Citation: 
Flynn PM, Taha TE, Cababasay M, Fowler MG, Mofenson LM, Owor M, Fiscus S, Stranix-Chibanda L, Coutsoudis A, Ganashanmugam D, Chakhtoura N, McCarthy K, ,Mukuzunga C, Makanani B, Moodley D, Nematadzira T, Kusakara B, Patil S, Vhembo T, Bobat R, Mmbaga BT, Masenya M, Nyati M, Theron G, Mulenga H, Butler K, Shapiro DE, PROMISE Study Team. Prevention of HIV-1 transmission through breastfeeding: efficacy of safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE): a randomized, open-label, clinical trial. J Acquir Immune Defic Syndr 2018 Apr 1:77(4):383-392. doi: 10.1097/QAI.0000000000001612. PMID: 29239901, PMCID: PMC5825265.
Collaborators: 
  • Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
  • Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA.
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
  • Elisabeth Glaser Pediatric AIDS Foundation, Washington, DC.
  • Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
  • Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.
  • Department of Paediatrics and Child Health, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
  • Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.
  • Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD.
  • Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
  • FHI 360, Durham, NC.
  • University of North Carolina-Lilongwe, Lilongwe, Malawi.
  • Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi.
  • Department of Obstetrics and Gynecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.
  • University of Zimbabwe-University of California, San Francisco, Harare, Zimbabwe.
  • Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
  • Department of Pediatrics, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
  • Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
  • Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa.
  • Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
  • George Clinic, Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.