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

April 11, 2014 updated by: French National Agency for Research on AIDS and Viral Hepatitis

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

1500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Burkina Faso
      • Ouagadougou, Burkina Faso
        • Université de Ouagadougou
  • South Africa
      • East London, South Africa
        • East London Hospital Complex
  • Uganda
      • Kampala, Uganda
        • Dept of Paediatrics and Child Health, Makerere University
  • Zambia
      • Lusaka, Zambia
        • Dept of Paediatrics and Child Health, School of Medicine, University of Zambia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 days to 1 week (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: A baby will be included if she/he:

  • is a singleton
  • is breastfed at day 7 by her/his mother and her/his mother intends to continue breastfeeding for at least 6 months
  • has a post-partum blood sample with a negative HIV-1 DNA PCR test result at day 7 (+/- 2 days)
  • has received ART as part of PMTCT

and if the mother:

  • has reached the local legal age for participating in medical research studies
  • is shown to be HIV-1 infected (with or without HIV-2 infection) and is not eligible for HAART or is not taking HAART
  • has received a perinatal antiretroviral prophylaxis during pregnancy and delivery,
  • has a CD4 count above the threshold of HAART initiation in pregnant women according to the national recommendation in each site (minimum 230 cells/µL),
  • resides within the study area and is not intending to move out of the area in the next year
  • gives assent for the infant to participate and gives consent to participate

Exclusion Criteria:

  • S/he presents clinical symptoms and/or biological abnormalities equal to or greater than grade II of the ANRS classification for adverse event on the day of enrolment
  • S/he presents with serious congenital malformation(s)
  • Her/his birth weight is lower than 2.0 kg
  • Her/his antiretroviral prophylaxis is extending beyond day 7
  • The mother has participated in the trial for a previous pregnancy
  • S/he and her/his mother are participating in another clinical trial on the day of enrolment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Acquisition of HIV-1 (as determined by HIV-1 DNA PCR)
Time Frame: between day 7 and 50 weeks of age
between day 7 and 50 weeks of age

Secondary Outcome Measures

Outcome Measure
Time Frame
HIV-1 free survival
Time Frame: at 50 weeks of age
at 50 weeks of age
HIV-1 free survival
Time Frame: at one year of age
at one year of age
safety of long-term prophylaxis
Time Frame: until 50 weeks of age
until 50 weeks of age
safety of long-term prophylaxis
Time Frame: until one year of age
until one year of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis

Collaborators

University of Bergen
The Research Council of Norway
European and Developing Countries Clinical Trials Partnership (EDCTP)
Université Montpellier
Swedish International Development Cooperation Agency (SIDA)

Investigators

  • 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)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

January 15, 2008

First Submitted That Met QC Criteria

March 20, 2008

First Posted (Estimate)

March 21, 2008

Study Record Updates

Last Update Posted (Estimate)

April 14, 2014

Last Update Submitted That Met QC Criteria

April 11, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 12174 PROMISE-PEP
  • EDCTP : RCN 183600

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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