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Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174

Nicolas Nagot123*, Chipepo Kankasa4, Nicolas Meda5, Justus Hofmeyr6, Cheryl Nikodem6, James K Tumwine7, Charles Karamagi78, Halvor Sommerfelt89, Dorine Neveu12, Thorkild Tylleskär8, Philippe Van de Perre123 and for the PROMISE-PEP group

Author affiliations

1 INSERM U 1058 and CHU, Montpellier, France

2 Universite Montpellier 1, Montpellier, France

3 Département de Bactériologie-Virologie et Département d’Information Médicale, CHU Montpellier, Montpellier, France

4 Department of Paediatrics and Child Health, University of Zambia, School of Medicine, Lusaka, Zambia

5 Centre of International Research for Health, Faculty of Health Sciences, University of Ouagadougou and Centre MURAZ, Bobo-Dioulasso, Burkina Faso

6 University of Western Cape, Cape Town, South Africa

7 Department of Paediatrics and Child Health, College of Health Sciences, School of Medicine Makerere University, Kampala, Uganda

8 Centre for International Health, University of Bergen, Bergen, Norway

9 Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway

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Citation and License

BMC Infectious Diseases 2012, 12:246  doi:10.1186/1471-2334-12-246

Published: 6 October 2012

Abstract

Background

Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.

Methods

The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.

HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.

The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks.

Discussion

This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.

Trial registration number ( http://www.clinicaltrials.gov webcite)

NCT00640263