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

This study has been completed.
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
The Research Council of Norway
Swedish International Development Cooperation Agency (SIDA)
Université Montpellier
University of Bergen
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier:
NCT00640263
First received: January 15, 2008
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: lopinavir/ritonavir (LPV/r)
Drug: Lamivudine (3TC)
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 1500
Study Start Date: December 2009
Study Completion Date: February 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   up to 9 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640263

Locations
Burkina Faso
Université de Ouagadougou
Ouagadougou, Burkina Faso
South Africa
East London Hospital Complex
East London, South Africa
Uganda
Dept of Paediatrics and Child Health, Makerere University
Kampala, Uganda
Zambia
Dept of Paediatrics and Child Health, School of Medicine, University of Zambia
Lusaka, Zambia
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
European and Developing Countries Clinical Trials Partnership (EDCTP)
The Research Council of Norway
Swedish International Development Cooperation Agency (SIDA)
Université Montpellier
University of Bergen
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)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier: NCT00640263     History of Changes
Other Study ID Numbers: ANRS 12174 PROMISE-PEP, EDCTP : RCN 183600
Study First Received: January 15, 2008
Last Updated: April 11, 2014
Health Authority: South Africa: Medicines Control Council
Zambia: Ministry of Health
Uganda: National Council for Science and Technology
Burkina Faso: Ministry of Health

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV-1
Breastfeeding
Prevention
lamivudine
lopinavir/ritonavir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Lamivudine
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 28, 2014