Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: Raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

S. Lambert-Niclot, E. C. George, A. Pozniak, E. White, C. Schwimmer, H. Jessen, M. Johnson, D. Dunn, C. F. Perno, B. Clotet, A. Plettenberg, A. Blaxhult, L. Palmisano, L. Wittkop, V. Calvez, A. G. Marcelin, F. Raffi, Nikos Dedes, Geneviève Chěne, Clotilde AllavenaBrigitte Autran, Andrea Antinori, Raffaella Bucciardini, Stefano Vella, Andrzej Horban, Jose Arribas, Abdel G. Babiker, Marta Boffito, Deenan Pillay, Anton Pozniak, Xavier Franquet, Siegfried Schwarze, Jesper Grarup, Aurélie Fischer, Laura Richert, Cédrick Wallet, François Raffi, Alpha Diallo, Jean Michel Molina, Juliette Saillard, Christiane Moecklinghoff, Hans Jürgen Stellbrink, Remko Van Leeuwen, Jose Gatell, Eric Sandstrom, Markus Flepp, Fiona Ewings, Elizabeth C. George, Fleur Hudson, Gillian Pearce, Romina Quercia, Felipe Rogatto, Randi Leavitt, Bach Yen Nguyen, Frank Goebel, Simone Marcotullio, Navrup Kaur, Peter Sasieni, Christina Spencer-Drake, Tim Peto, Veronica Miller, Fabien Arnault, Céline Boucherie, Delphine Jean, Virginie Paniego, Felasoa Paraina, Elodie Rouch, Christine Schwimmer, Malika Soussi, Audrey Taieb, Monique Termote, Guillaume Touzeau, Adam Cursley, Wendy Dodds, Anne Hoppe, Ischa Kummeling, Filippo Pacciarini, Nick Paton, Charlotte Russell, Kay Taylor, Denise Ward, Bitten Aagaard, Marius Eid, Daniela Gey, Birgitte Gram Jensen, Marie Louise Jakobsen, Per O. Jansson, Karoline Jensen, Zillah Maria Joensen, Ellen Moseholm Larsen, Christiane Pahl, Mary Pearson, Birgit Riis Nielsen, Søren Stentoft Reilev, Ilse Christ, Desiree Lathouwers, Corry Manting, Bienvenu Yves Mendy, Annie Metro, Sandrine Couffin-Cadiergues, Anne Laure Knellwolf, Lucia Palmisiano, Esther Aznar, Cristina Barea, Manuel Cotarelo, Herminia Esteban, Iciar Girbau, Beatriz Moyano, Miriam Ramirez, Carmen Saiz, Isabel Sanchez, Maria Yllescas, Andrea Binelli, Valentina Colasanti, Maurizio Massella, Olga Anagnostou, Vicky Gioukari, Giota Touloumi, Brigitte Schmied, Armin Rieger, Norbert Vetter, Stephane De Wit, Eric Florence, Linos Vandekerckhove, Jan Gerstoft, Lars Mathiesen, Christine Katlama, Andre Cabie, Antoine Cheret, Michel Dupon, Jade Ghosn, Pierre Marie Girard, Cécile Goujard, Yves Lévy, Philippe Morlat, Didier Neau, Martine Obadia, Philippe Perre, Jacques Reynes, Pierre Tattevin, Jean Marie Ragnaud, Laurence Weiss, Yazdanpanah Yazdan, Patrick Yeni, David Zucman, Georg Behrens, Stefan Esser, Gerd Fätkenheuer, Christian Hoffmann, Heiko Jessen, Jürgen Rockstroh, Reinhold Schmidt, Christoph Stephan, Stefan Unger, Angelos Hatzakis, George L. Daikos, Antonios Papadopoulos, Athamasios Skoutelis, Denes Banhegyi, Paddy Mallon, Fiona Mulcahy, Massimo Andreoni, Stefano Bonora, Francesco Castelli, Antonella D Arminio Monforte, Giovanni Di Perri, Massimo Galli, Adriano Lazzarin, Francesco Mazzotta, Torti Carlo, Vincenzo Vullo, Jan Prins, Clemens Richter, Dominique Verhagen, Arne Van Eeden, Manuela Doroana, Francisco Antunes, Fernando Maltez, Rui Sarmento-Castro, Juan Gonzalez Garcia, José López Aldeguer, Bonaventura Clotet, Pere Domingo, Jose M. Gatell, Hernando Knobel, Manuel Marquez, Martin Pilar Miralles, Joaquin Portilla, Vicente Soriano, Maria Jesus Tellez, Anders Thalme, Anders Blaxhult, Magnus Gisslen, Alan Winston, Julie Fox, Mark Gompels, Elbushra Herieka, Margaret Johnson, Clifford Leen, Alastair Teague, Ian Williams, Mark Alastair Boyd, Nina Friis Møller, Ellen Frøsig Moseholm Larsen, Lionel Piroth, Vincent Le Moing, Ferdinand W N M Wit, Justyna Kowalska, Juan Berenguer, Santiago Moreno, Nicolas J. Müller, Estée Török, Frank Post, Brian Angus, Vincent Calvez, Charles Boucher, Simon Collins, David Dunn, Sidonie Lambert, Anne Geneviève Marcelin, Carlo Federico Perno, Ellen White, Adriana Ammassari, Wolgang Stoehr, Reinhold Ernst Schmidt, Michal Odermarsky, Colette Smith, Rodolphe Thiébaut, Jose Ignacio Bernardino De La Serna, Antonella Castagna, Hans Jackob Furrer, Amanda Mocroft, Peter Reiss, Vincenzo Fragola, Marco Lauriola, Rita Murri, Pythia Nieuwkerk, Bruno Spire, Alain Volny-Anne, Brian West, Hélène Amieva, Josep Maria Llibre Codina, Marco Braggion, Emanuele Focá

Research output: Contribution to journalArticle

Abstract

Objectives: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Methods: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. Results: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of TREND = 0.007). Of note, 4/15 participants with IN RAM had a VL <200 copies/mL at time of testing. Conclusions: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.

Original languageEnglish
Article numberdkv427
Pages (from-to)1056-1062
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Lambert-Niclot, S., George, E. C., Pozniak, A., White, E., Schwimmer, C., Jessen, H., Johnson, M., Dunn, D., Perno, C. F., Clotet, B., Plettenberg, A., Blaxhult, A., Palmisano, L., Wittkop, L., Calvez, V., Marcelin, A. G., Raffi, F., Dedes, N., Chěne, G., ... Focá, E. (2016). Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: Raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART. Journal of Antimicrobial Chemotherapy, 71(4), 1056-1062. [dkv427]. https://doi.org/10.1093/jac/dkv427