TY - JOUR
T1 - Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and Côte d'Ivoire
T2 - The MONOD ANRS 12206 non-inferiority randomised trial
AU - Dahourou, Désiré Lucien
AU - Amorissani-Folquet, Madeleine
AU - Malateste, Karen
AU - Amani-Bosse, Clarisse
AU - Coulibaly, Malik
AU - Seguin-Devaux, Carole
AU - Toni, Thomas
AU - Ouédraogo, Rasmata
AU - Blanche, Stéphane
AU - Yonaba, Caroline
AU - Eboua, François
AU - Lepage, Philippe
AU - Avit, Divine
AU - Ouédraogo, Sylvie
AU - Van de Perre, Philippe
AU - N'Gbeche, Sylvie
AU - Kalmogho, Angèle
AU - Salamon, Roger
AU - Meda, Nicolas
AU - Timité-Konan, Marguerite
AU - Leroy, Valériane
AU - Désiré Lucien Dahourou, Lucien Dahourou
AU - Colette Ouédraogo, Ouédraogo
AU - Sawadogo, Mamadou
AU - Wilfried Somé, Somé
AU - Désiré Sondo, Sondo
AU - Thio, Elisabeth
AU - Barry, Mamadou
AU - Hiembo, William
AU - Fla Kouéta, Kouéta
AU - Ouattara, Adama
AU - Moussa Ouédraogo, Ouédraogo
AU - Rasmata Ouédraogo, Ouédraogo
AU - Sylvie Ouédraogo, Ouédraogo
AU - Congo, Bernadette
AU - Barry, Rose
AU - Yé, Diarra
AU - Congo, Malika
AU - Edouard Minéné, Minéné
AU - Coulibaly, Marie
AU - Angèle Kalmogho, Pierre Innocent Guissou
AU - Kam, Ludovic
AU - Emile Ouédraogo, Ouédraogo
AU - Lassana Sangaré, Sangaré
AU - Tiendrebeogo, Sylvestre
AU - Ky-Zerbo, Odette
AU - Anglaret, Xavier
AU - Clarisse Amani-Bossé, Amani-Bossé
AU - Devaux, Carole
AU - Schmit, Jean Claude
AU - on behalf of the MONOD Study Group
N1 - Funding Information:
We thank the children, their families and the staff from all participating centres for their dedication. We warmly thank Andrea Ciaranello for her helpful comments on an early draft, Valérie Journot for her helpful statistical advice, and Sophie Desmonde for editing. We thank the MONOD ANRS 12206 trial independent data monitoring committee meeting: Dominique Costagliola (Chair; Paris, France), Mark Cotton (Cape Town, South Africa), Carlo Giaquito (Bologna, Italie), Diana Gibb (London, UK) and Elisabeth Menu (Paris, France). Désiré Dahourou PhD was funded by the ANRS (ANRS12206-B89). Malik Coulibaly PhD was funded by EDCTP-ANRS-LIH. The ANRS 12206 MONOD Collaboration Study Group (as of 7 July 2015): Participating sites. Burkina Faso, Ouagadougou: Centre de Recherche International pour la Santé: Malik Coulibaly, Désiré Lucien Dahourou, Nicolas Meda (co-investigator), Colette Ouédraogo, Mamadou Sawadogo, Wilfried Somé, Désiré Sondo, Elisabeth Thio.
Publisher Copyright:
© The Author(s). 2017.
PY - 2017/4/24
Y1 - 2017/4/24
N2 - Background: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years. Methods: The MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, CÔte d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 1215 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).
AB - Background: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years. Methods: The MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, CÔte d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 1215 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).
KW - Africa
KW - Early antiretroviral treatment
KW - Efavirenz
KW - HIV
KW - Infants
KW - Lopinavir
KW - Protease inhibitors
KW - Randomised clinical trial
KW - Treatment simplification
KW - Virological outcomes
UR - http://www.scopus.com/inward/record.url?scp=85018243501&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/28434406
U2 - 10.1186/s12916-017-0842-4
DO - 10.1186/s12916-017-0842-4
M3 - Article
C2 - 28434406
AN - SCOPUS:85018243501
SN - 1741-7015
VL - 15
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 85
ER -