title: Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174.
abstract: BACKGROUND
  Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.
  
  
  METHODS
  The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks.
  
  
  CONCLUSIONS
  This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.
authors.affiliation: INSERM U 1058 and CHU, Montpellier, France. n-nagot@chu-montpellier.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Chipepo
authors.initials: C
authors.lastname: Kankasa
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meda
authors.forename: Justus
authors.initials: J
authors.lastname: Hofmeyr
authors.forename: Cheryl
authors.initials: C
authors.lastname: Nikodem
authors.forename: James K
authors.initials: JK
authors.lastname: Tumwine
authors.forename: Charles
authors.initials: C
authors.lastname: Karamagi
authors.forename: Halvor
authors.initials: H
authors.lastname: Sommerfelt
authors.forename: Dorine
authors.initials: D
authors.lastname: Neveu
authors.forename: Thorkild
authors.initials: T
authors.lastname: Tylleskär
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
mesh_terms: D000349:Africa; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001942:Breast Feeding; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D061466:Lopinavir / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011247:Pregnancy; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019259:Lamivudine; D019438:Ritonavir