Prevention of HIV-1 Transmission Through Breastfeeding: Efficacy and 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.

Abstract

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.

• Authors: Patricia M Flynn, Taha E Taha, Mae Cababasay, Mary Glenn Fowler, Lynne M Mofenson, Maxensia Owor, Susan Fiscus, Lynda Stranix-Chibanda, Anna Coutsoudis, Devasena Gnanashanmugam, Nahida Chakhtoura, Katie McCarthy, Cornelius Mukuzunga, Bonus Makanani, Dhayendre Moodley, Teacler Nematadzira, Bangini Kusakara, Sandesh Patil, Tichaona Vhembo, Raziya Bobat, Blandina T Mmbaga, Maysseb Masenya, Mandisa Nyati, Gerhard Theron, Helen Mulenga, Kevin Butler, David E Shapiro, PROMISE Study Team
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 77 Issue 4 Pg. 383-392 (04 01 2018) ISSN: 1944-7884 [Electronic] United States
• PMID: 29239901 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents

Topics

• Africa South of the Sahara
• Anti-HIV Agents (therapeutic use)
• Breast Feeding
• Chemoprevention (methods)
• Child, Preschool
• Female
• HIV Infections (drug therapy, pathology, prevention & control, transmission)
• Humans
• India
• Infant
• Infant, Newborn
• Infectious Disease Transmission, Vertical (prevention & control)
• Postpartum Period
• Treatment Outcome