Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
NCT ID: NCT00640263
Last Updated: 2014-04-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
1500 participants
INTERVENTIONAL
2009-12-31
2014-02-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Infant Peri-Exposure Prophylaxis to Prevent HIV-1 Transmission by Breastfeeding: Mechanisms & Safety
NCT03519503
Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding
NCT00074412
Universal Use of EFV-TDF-FTC and AZT-3TC-LPV/r Combinations for HIV-1 PMTCT in Pregnant and Breastfeeding Women : a Phase 3 Trial
NCT00936195
A Study of Zidovudine/Lamivudine and Either Nevirapine or Nelfinavir for Reduction of Mother-to-child HIV Transmission During Breastfeeding
NCT00146380
Trizivir Vs. Kaletra and Combivir for the Prevention of Mother-to-Child Transmission of HIV
NCT00270296
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
infant peri-exposure prophylaxis with lopinavir/ritonavir
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.
2
infant peri-exposure prophylaxis with lamivudine
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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 Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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 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
5 Days
9 Days
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
European and Developing Countries Clinical Trials Partnership (EDCTP)
OTHER_GOV
The Research Council of Norway
OTHER
Swedish International Development Cooperation Agency (SIDA)
OTHER_GOV
Université Montpellier
OTHER
University of Bergen
OTHER
French National Agency for Research on AIDS and Viral Hepatitis
OTHER_GOV
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Philippe Vande Perre, MD, PhD
Role: STUDY_CHAIR
University of Montpellier, France
Thorkild Tylleskär, MD, PhD
Role: STUDY_CHAIR
Centre For International Health
Nicolas Meda, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Ouagadougou, Burkina Faso
James K Tumwine, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Dept of Paediatrics and Child Health, Makerere University, Uganda
Chipepo Kankasa, MD
Role: PRINCIPAL_INVESTIGATOR
Dept of Paediatrics and Child Health, School of Medicine, University of Zambia
Justus Hofmeyer, MD
Role: PRINCIPAL_INVESTIGATOR
East London Hospital Complex
Eva-Charlotte Ekström, PhD
Role: PRINCIPAL_INVESTIGATOR
Uppsala University, Uppsala, Sweden
Stephane Blanche, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hôpital Necker Enfants Malades, Université Paris V (EA 3620)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Université de Ouagadougou
Ouagadougou, , Burkina Faso
East London Hospital Complex
East London, , South Africa
Dept of Paediatrics and Child Health, Makerere University
Kampala, , Uganda
Dept of Paediatrics and Child Health, School of Medicine, University of Zambia
Lusaka, , Zambia
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Kourtis AP, Jamieson DJ, de Vincenzi I, Taylor A, Thigpen MC, Dao H, Farley T, Fowler MG. Prevention of human immunodeficiency virus-1 transmission to the infant through breastfeeding: new developments. Am J Obstet Gynecol. 2007 Sep;197(3 Suppl):S113-22. doi: 10.1016/j.ajog.2007.03.003.
Birungi N, Fadnes LT, Engebretsen IMS, Tumwine JK, Astrom AN; for ANRS 12174 AND 12341 study groups. Antiretroviral treatment and its impact on oral health outcomes in 5 to 7 year old Ugandan children: A 6 year follow-up visit from the ANRS 12174 randomized trial. Medicine (Baltimore). 2020 Sep 25;99(39):e22352. doi: 10.1097/MD.0000000000022352.
Birungi N, Fadnes LT, Engebretsen IMS, Lie SA, Tumwine JK, Astrom AN; ANRS 12174 and 12341 study groups. Caries experience and oral health related quality of life in a cohort of Ugandan HIV-1 exposed uninfected children compared with a matched cohort of HIV unexposed uninfected children. BMC Public Health. 2020 Mar 30;20(1):423. doi: 10.1186/s12889-020-08564-1.
Montoya-Ferrer A, Sanosyan A, Fayd'herbe de Maudave A, Pisoni A, Bollore K, Moles JP, Peries M, Tylleskar T, Tumwine JK, Ndeezi G, Gorgolas M, Nagot N, van de Perre P, Tuaillon E. Clinical and Biological Factors Associated With Early Epstein-Barr Virus Infection in Human Immunodeficiency Virus-Exposed Uninfected Infants in Eastern Uganda. Clin Infect Dis. 2021 Mar 15;72(6):1026-1032. doi: 10.1093/cid/ciaa161.
Birungi N, Fadnes LT, Engebretsen IMS, Lie SA, Tumwine JK, Astrom AN; ANRS 12174 and 12341 study groups. Association of maternal HIV-1 severity with dental caries: an observational study of uninfected 5- to 7-yr-old children of HIV-1-infected mothers without severe immune suppression. Eur J Oral Sci. 2020 Feb;128(1):46-54. doi: 10.1111/eos.12669. Epub 2020 Jan 29.
Kariyawasam D, Peries M, Foissac F, Eymard-Duvernay S, Tylleskar T, Singata-Madliki M, Kankasa C, Meda N, Tumwine J, Mwiya M, Engebretsen I, Fluck CE, Hartmann MF, Wudy SA, Hirt D, Treluyer JM, Moles JP, Blanche S, Van De Perre P, Polak M, Nagot N; ANRS 12174 Trial Group. Lopinavir-Ritonavir Impairs Adrenal Function in Infants. Clin Infect Dis. 2020 Aug 14;71(4):1030-1039. doi: 10.1093/cid/ciz888.
Blanche S, Tylleskar T, Peries M, Kankasa C, Engebretsen I, Meda N, Tumwine JK, Singata-Madliki M, Mwiya M, Van de Perre P, Nagot N; ANRS 12174 Trial Group. Growth in HIV-1-exposed but uninfected infants treated with lopinavir-ritonavir versus lamivudine: a secondary analysis of the ANRS 12174 trial. Lancet HIV. 2019 May;6(5):e307-e314. doi: 10.1016/S2352-3018(18)30361-8. Epub 2019 Feb 24.
Some EN, Engebretsen IMS, Nagot N, Meda N, Lombard C, Vallo R, Peries M, Kankasa C, Tumwine JK, Hofmeyr GJ, Singata M, Harper K, Van De Perre P, Tylleskar T; ANRS 12174 Trial Group. Breastfeeding patterns and its determinants among mothers living with Human Immuno-deficiency Virus -1 in four African countries participating in the ANRS 12174 trial. Int Breastfeed J. 2017 May 2;12:22. doi: 10.1186/s13006-017-0112-2. eCollection 2016.
Foissac F, Blume J, Treluyer JM, Tylleskar T, Kankasa C, Meda N, Tumwine JK, Singata-Madliki M, Harper K, Illamola SM, Bouazza N, Nagot N, Van de Perre P, Blanche S, Hirt D. Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01869-16. doi: 10.1128/AAC.01869-16. Print 2017 Feb.
Nagot N, Kankasa C, Tumwine JK, Meda N, Hofmeyr GJ, Vallo R, Mwiya M, Kwagala M, Traore H, Sunday A, Singata M, Siuluta C, Some E, Rutagwera D, Neboua D, Ndeezi G, Jackson D, Marechal V, Neveu D, Engebretsen IMS, Lombard C, Blanche S, Sommerfelt H, Rekacewicz C, Tylleskar T, Van de Perre P; ANRS 12174 Trial Group. Extended pre-exposure prophylaxis with lopinavir-ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial. Lancet. 2016 Feb 6;387(10018):566-573. doi: 10.1016/S0140-6736(15)00984-8. Epub 2015 Nov 19.
Nagot N, Kankasa C, Meda N, Hofmeyr J, Nikodem C, Tumwine JK, Karamagi C, Sommerfelt H, Neveu D, Tylleskar T, Van de Perre P; PROMISE-PEP group. Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174. BMC Infect Dis. 2012 Oct 6;12:246. doi: 10.1186/1471-2334-12-246.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
EDCTP : RCN 183600
Identifier Type: -
Identifier Source: secondary_id
ANRS 12174 PROMISE-PEP
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.