title: Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes.
  
  
  METHODS
  Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates.
  
  
  RESULTS
  Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms.
  
  
  CONCLUSIONS
  This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
authors.affiliation: *Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; †Maternal Adolescent and Child Health, University of the Witwatersrand, South Africa; ‡Fred Hutchinson Cancer Research Center, Seattle, WA; §Department of Pediatrics, Stanford University School of Medicine, Stanford, CA; ‖Department of Obstetrics and Gynecology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe; ¶Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; #Makerere University, Johns Hopkins University, Research Collaboration, Kampala, Uganda; **Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; ††Department of Pediatrics, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe; ‡‡Department of Global Health and Population, Harvard University School of Public Health, Boston, MA; §§Family Health International, Research Triangle Park, NC; ‖‖Division of HIV/AIDS, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD; and ¶¶Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
authors.forename: Mary Glenn
authors.initials: MG
authors.lastname: Fowler
authors.forename: Hoosen
authors.initials: H
authors.lastname: Coovadia
authors.forename: Casey M
authors.initials: CM
authors.lastname: Herron
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Maldonado
authors.forename: Tsungai
authors.initials: T
authors.lastname: Chipato
authors.forename: Dhayendre
authors.initials: D
authors.lastname: Moodley
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.forename: Jim
authors.initials: J
authors.lastname: Aizire
authors.forename: Karim
authors.initials: K
authors.lastname: Manji
authors.forename: Lynda
authors.initials: L
authors.lastname: Stranix-Chibanda
authors.forename: Wafaie
authors.initials: W
authors.lastname: Fawzi
authors.forename: Vani
authors.initials: V
authors.lastname: Chetty
authors.forename: Lindiwe
authors.initials: L
authors.lastname: Msweli
authors.forename: Rodrick
authors.initials: R
authors.lastname: Kisenge
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brown
authors.forename: Anthony
authors.initials: A
authors.lastname: Mwatha
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Melissa
authors.initials: M
authors.lastname: Allen
authors.forename: Kathleen
authors.initials: K
authors.lastname: George
authors.forename: Philip
authors.initials: P
authors.lastname: Andrew
authors.forename: Sheryl
authors.initials: S
authors.lastname: Zwerski
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: J Brooks
authors.initials: JB
authors.lastname: Jackson
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001942:Breast Feeding; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D019829:Nevirapine