Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      The ANRS 12174 study is a clinical trial that will compare the efficacy and safety of
      prolonged infant peri-exposure prophylaxis (PEP) with Lopinavir/Ritonavir (LPV/r) versus
      Lamivudine to prevent HIV-1 transmission through breast milk in children born to
      HIV-1-infected mothers not eligible for HAART and having benefited from perinatal
      antiretroviral (ART) regimens. The study will recruit 1500 mother-infant pairs in 4 African
      countries.

      Study design:

      PROMISE PEP is a multinational, randomised double-blind controlled clinical trial.

      Intervention:

      Infants will be randomised to receive LPV/r or 3TC twice daily from day seven (± 2 days)
      after birth until 4 weeks after cessation of breastfeeding (BF). We will recommend exclusive
      BF (EBF) up till including the 26th week of life followed by a relatively rapid (maximum of 8
      weeks) cessation period. The maximum duration of PEP will thereby be 38 weeks.

      Primary objective:

      To compare the efficacy of infant LPV/r (40/10mg twice daily if 2-4kg and 80/20mg twice daily
      if >4kg) vs. Lamivudine 7,5mg twice daily if 2-4kg, 25mg twice daily if 4-8kg and 50mg twice
      daily if >8kg) from day 7 until 4 weeks after cessation of BF (maximum duration of
      prophylaxis: 50 weeks for a maximum duration of breastfeeding of 46 weeks) to prevent
      postnatal HIV-1 acquisition between 7 days and 50 weeks of age.

      Secondary objectives:

        -  To assess the safety of long-term infant prophylaxis with LPV/r versus Lamivudine
           (including resistance, adverse events and growth) until 50 weeks.

        -  HIV-1-free survival until 50 weeks

        -  To build clinical trials capacity at the four study sites.

      Main endpoint:

      Acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age

      Study population:

      HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for
      HAART who choose to breastfeed their infants and who have benefited from the national
      prevention of mother to child transmission (PMTCT) program during pregnancy and delivery. The
      study will recruit 1500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia.

      Study duration:

      Infants will be followed up for 50 weeks and the total study duration is five years.

      Expected outcome:

      This study will inform on the relative advantages (efficacy) and drawbacks of two
      interventions to support HIV-1-infected women not eligible for HAART to safely breastfeed
      their babies. If found to be safe and efficacious, the regimens would avoid the existing
      contradiction between optimal infant feeding and the prevention of MTCT through breast milk.
      Clinical trial capacity development will improve the future quality of trials conducted in
      these countries.
    


Intervention name(s): lopinavir/ritonavir (LPV/r); Lamivudine (3TC)
Intervention type(s): Drug; Drug
Intervention description(s): Oral liquid formulation lopinavir/ritonavir(80 mg lopinavir + 20 mg ritonavir/mL); Dosing : 40/10mg twice daily if infant weight is between 2 to 4 kg and 80/20mg twice daily if infant weight is above 4kg The lopinavir/ritonavir will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.; Oral liquid solution lamivudine(10 mg/mL). Dosing : 7,5 mg twice daily if if infant weight is between 2 to 4 kg ; 25 mg twice daily if infant weight is between 4 to 8 kg ; 50 mg twice daily if infant weight is above 8kg.
The lamivudine will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: HIV-1; Breastfeeding; Prevention; lamivudine; lopinavir/ritonavir