A randomised controlled trial comparing the efficacy of infant peri-exposure prophylaxis with Lopinavir/Ritonavir (LPV/r) versus Lamivudine to prevent HIV-1 transmission by breastfeeding.
Full project title: PROMISE PEP: Prevention of mother to child transmission of HIV
Coordinators: Philippe Van de Perre / Thorkild Tylleskär
Period: 2008-2012
Funding:
Research Council of Norway
The European & Developing Countries Clinical Trials Partnership
ANRS
Responsible unit: University of Montpellier 1
Relevant links: EDCTP website
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 ANRS 12174 is a multinational, randomised controlled clinical trial. Intervention Infants will be randomised to receive LPV/r or Lamivudine twice daily from day 7 (± 2 days) after birth until 4 weeks after cessation of breastfeeding (maximum duration of prophylaxis: 50 weeks for a maximum duration of breastfeeding of 46 weeks), as two PEP interventions to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age. We will recommend exclusive breastfeeding (EBF) until 26th week of life followed by a cessation period of 8 weeks maximum in both arms.
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 Seronegative 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 for 46 weeks. 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.
For more information and list of publications see ClinicalTrials.gov