Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
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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 |
- 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 ]
Estimated Enrollment: | 1500 |
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) |
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. |
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Ages Eligible for Study: | up to 9 Days |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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
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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 |
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) |
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Additional Information:
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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: | November 7, 2012 |
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:
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Lamivudine Ritonavir |
Lopinavir Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents HIV Protease Inhibitors Protease Inhibitors |
ClinicalTrials.gov processed this record on March 14, 2013