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

Sidonie Lambert-Niclot, E. C. George, A. Pozniak, E. White, Christine Schwimmer, H. Jessen, M. Johnson, D. Dunn, C. F. Perno, B. Clotet, Andreas Plettenberg, A. Blaxhult, Lucia Palmisano, Linda Wittkop, V. Calvez, A. G. Marcelin, F. Raffi, N. Dedes, Genevieve Chene, Clotilde AllavenaBrigitte Autran, Andrea Antinori, R. Bucciardini, S. Vella, A. Horban, J. Arribas, Abdel Babiker, Marta Boffito, Deenan Pillay, A. Pozniak, Xavier Franquet, Siegfried Schwarze, Jesper Grarup, Aurélie Fischer, L. Richert, Cédrick Wallet, F. Raffi, Alpha Diallo, Jean Michel Molina, Juliette Saillard, Christiane Moecklinghoff, H. J. Stellbrink, Remko Van Leeuwen, J. M. Gatell, E. Sandström, Markus Flepp, Fiona Ewings, Elizabeth C. George, F. Hudson, Gillian Pearce, Romina Quercia, Felipe Rogatto, Randi Leavitt, Bach Yen Nguyen, Frank Goebel, Simone Marcotullio, Navrup Kaur, Peter Sasieni, Christina Spencer-Drake, T. E A 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 Olof Jansson, Karoline Jensen, Zillah Maria Joensen, Ellen Moseholm Larsen, Christiane Pahl, Mary Pearson, Birgit Riis Nielsen, Søren 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, B. Schmied, Armin Rieger, N. Vetter, Stéphane De Wit, E. Florence, L. Vandekerckhove, J. Gerstoft, L. Mathiesen, Christine Katlama, A. Cabié, Antoine Cheret, M. Dupon, Jade Ghosn, Pierre Marie Girard, C. Goujard, Y. Levy, P. Morlat, D. Neau, Martine Obadia, Philippe Perre, Jacques Reynes, Pierre Tattevin, J. M. Ragnaud, L. Weiss, Yazdanpanah Yazdan, P. Yeni, David Zucman, G. Behrens, S. Esser, Gerd Fätkenheuer, Christian Hoffmann, Heiko Jessen, J. Rockstroh, Reinhold Schmidt, Christoph Stephan, Stefan Unger, A. Hatzakis, G. L. Daikos, Antonios Papadopoulos, Athamasios Skoutelis, Dénes Bánhegyi, Patrick W. Mallon, F. Mulcahy, M. Andreoni, S. Bonora, F. Castelli, Antonella D. Monforte, Giovanni Di Perri, Massimo Galli, Adriano Lazzarin, F. Mazzotta, Torti Carlo, Vincenzo Vullo, J. M. Prins, C. Richter, Dominique Verhagen, A. van Eeden, M. Doroana, Francisco Antunes, F. Maltez, Rui Sarmento-Castro, Juan Gonzalez Garcia, José López Aldeguer, Bonaventura Clotet, P. Domingo, Jose M. Gatell, H. Knobel, Manuel Marquez, Martin Pilar Miralles, Joaquín Portilla, Vicente Soriano, Maria Jesus Tellez, A. Thalme, A. Blaxhult, Magnus Gisslén, Alan Winston, Julie Fox, M. M. Gompels, Elbushra Herieka, Margaret Johnson, C. Leen, Alastair Teague, Ian Williams, Mark Alastair Boyd, Nina Friis Moller, Ellen Frøsig Moseholm Larsen, Lionel Piroth, Vincent Le Moing, Ferdinand Wit, Justyna Kowalska, Juan Berenguer, Santiago Moreno, N. Müller, Estée Török, Frank A. Post, Brian Angus, V. Calvez, C. A B Boucher, Simon Collins, D. Dunn, Sidonie Lambert, Anne Geneviève Marcelin, Carlo Federico Perno, Ellen White, Adriana Ammassari, Wolgang Stoehr, Reinhold Ernst Schmidt, Michal Odermarsky, Colette Smith, Rodolphe Thiebaut, Jose Ignacio Bernardino De La Serna, Antonella Castagna, Hans Jackob Furrer, Amanda Mocroft, Peter Reiss, V. Fragola, Marco Lauriola, R. Murri, Pythia Nieuwkerk, B. Spire, Alain Volny-Anne, Brian West, H. Amieva, Josep Maria Llibre Codina, Marco Braggion, Emanuele Focà

Research output: Contribution to journalArticlepeer-review

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

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this