Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
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.
PROMISE PEP is a multinational, randomised double-blind controlled clinical trial.
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.
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.
- 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.
Acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age
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.
Infants will be followed up for 50 weeks and the total study duration is five years.
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.
Drug: lopinavir/ritonavir (LPV/r)
Drug: Lamivudine (3TC)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||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|
- Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) [ Time Frame: between day 7 and 50 weeks of age ] [ Designated as safety issue: No ]
- HIV-1 free survival [ Time Frame: at 50 weeks of age ] [ Designated as safety issue: No ]
- HIV-1 free survival [ Time Frame: at one year of age ] [ Designated as safety issue: No ]
- safety of long-term prophylaxis [ Time Frame: until 50 weeks of age ] [ Designated as safety issue: Yes ]
- safety of long-term prophylaxis [ Time Frame: until one year of age ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
infant peri-exposure prophylaxis with lopinavir/ritonavir
Drug: lopinavir/ritonavir (LPV/r)
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.
Active Comparator: 2
infant peri-exposure prophylaxis with lamivudine
Drug: Lamivudine (3TC)
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.
|Université de Ouagadougou|
|Ouagadougou, Burkina Faso|
|East London Hospital Complex|
|East London, South Africa|
|Dept of Paediatrics and Child Health, Makerere University|
|Dept of Paediatrics and Child Health, School of Medicine, University of Zambia|
|Study Chair:||Philippe Vande Perre, MD, PhD||University of Montpellier, France|
|Study Chair:||Thorkild Tylleskär, MD, PhD||Centre For International Health|
|Principal Investigator:||Nicolas Meda, MD, PhD||University of Ouagadougou, Burkina Faso|
|Principal Investigator:||James K Tumwine, MD, PhD||Dept of Paediatrics and Child Health, Makerere University, Uganda|
|Principal Investigator:||Chipepo Kankasa, MD||Dept of Paediatrics and Child Health, School of Medicine, University of Zambia|
|Principal Investigator:||Justus Hofmeyer, MD||East London Hospital Complex|
|Principal Investigator:||Eva-Charlotte Ekström, PhD||Uppsala University, Uppsala, Sweden|
|Principal Investigator:||Stephane Blanche, MD, PhD||Hôpital Necker Enfants Malades, Université Paris V (EA 3620)|