Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding

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.

Conditions

• HIV Infections

Interventions

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.

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.

Sponsors & Collaborators

• European and Developing Countries Clinical Trials Partnership (EDCTP)

  collaborator OTHER_GOV

• The Research Council of Norway

  collaborator OTHER

• Swedish International Development Cooperation Agency (SIDA)

  collaborator OTHER_GOV

• Université Montpellier

  collaborator OTHER

• University of Bergen

  collaborator OTHER

• French National Agency for Research on AIDS and Viral Hepatitis

  lead OTHER_GOV

Principal Investigators

• Philippe Vande Perre, MD, PhD · University of Montpellier, France

• Thorkild Tylleskär, MD, PhD · Centre For International Health

• Nicolas Meda, MD, PhD · University of Ouagadougou, Burkina Faso

• James K Tumwine, MD, PhD · Dept of Paediatrics and Child Health, Makerere University, Uganda

• Chipepo Kankasa, MD · Dept of Paediatrics and Child Health, School of Medicine, University of Zambia

• Justus Hofmeyer, MD · East London Hospital Complex

• Eva-Charlotte Ekström, PhD · Uppsala University, Uppsala, Sweden

• Stephane Blanche, MD, PhD · Hôpital Necker Enfants Malades, Université Paris V (EA 3620)

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

5 Days

Max Age

9 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-12-31

Primary Completion

2013-05-31

Completion

2014-02-28

Countries

• Burkina Faso
• South Africa
• Uganda
• Zambia

Study Locations