Accès ouvert déclaré
2019
article
Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: a sub-study of the NEAT001/ANRS143 randomized trial
Laura Dickinson, Rohan Gurjar, Wolfgang Stöhr, Stefano Bonora, Andrew Owen, Antonio D’Avolio, Adam Cursley, Jean‐Michel Molina, Gerd Fäetkenheuer, Linos Vandekerckhove, Giovanni Di Perri, François Raffi, Marta Boffito, Nikos Dedes, Clotilde Allavena, Andrea Antinori, Raffaella Bucciardini, Stefano Vella, Andrzéj Horban, José Ramón Arribas, Abdel G. Babiker, Deenan Pillay, Siegfried Schwarze, Jesper Grarup, Aurélie Fischer, Laura Richert, Cédrick Wallet, Juliette Saillard, Christiane Moecklinghoff, Hans‐Jürgen Stellbrink, R VANLEEUWEN, José M. Gatell, Eric Sandström, Markus Flepp, Elizabeth C. George, Gillian Pearce, Romina Quercia, Felipe Rogatto, Randi Y. Leavitt, Bach-Yen Nguyen, F. D. Goebel, Simone Marcotullio, Veronica Miller, Peter Sasieni, Geneviève Chêne, F. Arnault, Céline Boucherie, Delphine Jean, Virginie Paniego, Felasoa Paraina, Elodie Rouch, Christine Schwimmer, M. Soussi, Audrey Taïeb, Monique Termote, Guillaume Touzeau, AbdelG Babiker, Wendy Dodds, Anne Hoppé, Ischa Kummeling, Filippo Pacciarini, Nick Paton, Charlotte Russell, Kay Taylor, Denise Ward, Bitten Aagaard, Marius Eid, Daniela Gey, Birgitte GramJensen, Marie-Louise Jakobsen, Per O Jansson, Karoline Jensen, Zillah MariaJoensen, Ellen Frøsig MoseholmLarsen, Christiane Pahl, Mary Pearson, Birgit Riis Nielsen, Søren Stentoft Reilev, Ilse Christ, Desiree Lathouwers, Corry Manting, Remko van Leeuwen, BienvenuYves Mendy, Annie Métro, S. Couffin-Cadiergues, Anne‐Laure Knellwolf, Lucia Palmisiano, E. Ubiña Aznar, Cristina Barea, Manuel Cotarelo, Herminia Esteban, Iciar Girbau, B. Moyano, Miriam Ramírez, Carmen Sáiz, Isabel Sánchez, María Yllescas, Andrea Binelli, Valentina Colasanti, Maurizio Massella, Olga Anagnostou, Vicky Gioukari, Giota Touloumi, Brigitte Schmied, Armin Rieger, N Vetter, Stephane DeWit, Éric Florence, Jan Gerstoft, Lars Mathiesen, Christine Katlama, André Cabie, Antoine Chéret, M. Dupon, Jade Ghosn, Pierre-Marie Girard, Cécile Goujard, Yves Lévy, Philippe Morlat, Didier Neau, Martine Obadia, Philippe Van de Perre, Lionel Piroth, Jacques Reynes, Pierre Tattevin, J.M. Ragnaud, Laurence Weiss, Yazdanpanah Yazdan, Patrick Yéni, David Zucman, Stefan Esser, Gerd Fätkenheuer, Christian Hoffmann, Heiko Jessen, Jürgen K. Rockstroh, Reinhold Schmidt, Christoph Stephan, Stefan Unger, Angelos Hatzakis, Antonios Papadopoulos, Athamasios Skoutelis, Dénes Bánhegyi, Fiona Mulcahy, Massimo Andreoni, Antonella d’Arminio Monforte, Giovanni DiPerri, Massimo Galli, Adriano Lazzarin, Francesco Mazzotta, Carlo Torti, Vincenzo Vullo, Jan M. Prins, Clemens Richter, D.W.M. Verhagen, Arne VanEeden, Manuela Doroana, Francisco Antunes, Fernando Maltêz, Rui Sarmento‐Castro, Juan González‐García, José López Aldeguer, Bonaventura Clotet, Peré Domingo, Hernando Knobel, Manuel Marquez, Martin PilarMiralles, Joaquín Portilla, MariaJesus Tellez, Anders Thalme, Anders Blaxhult, Magnus Gisslén, Alan Winston, Julie Fox, Mark Gompels, E Herieka, Margaret Johnson, Clifford Leen, Alastair Teague, Ian Williams, M. W. J. Boyd, Nina Friis‐Møller, Vincent Le Moing, Ferdinand W N M Wit, Justyna Kowalska, Juan Berenguer, Santiago Moreno, N Müller, M. Estée Török, Frank A. Post, Brian Angus, Vincent Cálvez, Charles A. Boucher, Simon Collins, David Dunn, Sidonie Lambert, Anne‐Geneviève Marcelin, Carlo Federico Perno, Ellen White, Adriana Ammassari, Michal Odermarsky, Colette Smith, Rodolphe Thiébaut, Jose Ignacio Bernardino DeLaSerna, Antonella Castagna, Stéphane De Wit, Hans-Jackob Furrer, Amanda Mocroft, Peter Reiss, Vincenzo Fragola, Marco Lauriola, Rita Murri, Pythia T. Nieuwkerk, Bruno Spire, Alain Volny‐Anne, Brian West, Hélène Amieva, JosepMaria Llibre Codina, Marco Braggion, Emanuele Focà
9Citations signalées — pas une note de qualité
14Institutions déclarées
5Pays d’affiliation déclarés
Résumé fourni par la source
OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P<0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P=0.269; and 1.82 (0.61-5.41), P=0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.
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Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: a sub-study of the NEAT001/ANRS143 randomized trial
- Date Crossref
- 21/11/2019
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
HIV/AIDS drug development and treatmentHIV-related health complications and treatmentsPharmacogenetics and Drug Metabolism