title: Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months.
  
  
  METHODS
  In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412.
  
  
  RESULTS
  Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.
  
  
  CONCLUSIONS
  Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.
  
  
  BACKGROUND
  US National Institutes of Health.
authors.affiliation: Maternal Adolescent and Child Health (MatCH), University of the Witwatersrand, Johannesburg, South Africa. hcoovadia@match.org.za
authors.forename: Hoosen M
authors.initials: HM
authors.lastname: Coovadia
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Brown
authors.forename: Mary Glenn
authors.initials: MG
authors.lastname: Fowler
authors.forename: Tsungai
authors.initials: T
authors.lastname: Chipato
authors.forename: Dhayendre
authors.initials: D
authors.lastname: Moodley
authors.forename: Karim
authors.initials: K
authors.lastname: Manji
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.forename: Lynda
authors.initials: L
authors.lastname: Stranix-Chibanda
authors.forename: Vani
authors.initials: V
authors.lastname: Chetty
authors.forename: Wafaie
authors.initials: W
authors.lastname: Fawzi
authors.forename: Clemensia
authors.initials: C
authors.lastname: Nakabiito
authors.forename: Lindiwe
authors.initials: L
authors.lastname: Msweli
authors.forename: Roderick
authors.initials: R
authors.lastname: Kisenge
authors.forename: Laura
authors.initials: L
authors.lastname: Guay
authors.forename: Anthony
authors.initials: A
authors.lastname: Mwatha
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Lynn
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Kathleen
authors.initials: K
authors.lastname: George
authors.forename: Philip
authors.initials: P
authors.lastname: Andrew
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Sheryl
authors.initials: S
authors.lastname: Zwerski
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Maldonado
mesh_terms: D000284:Administration, Oral; D000328:Adult; D017954:Africa South of the Sahara; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000008:administration & dosage*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine