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, C. 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

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Abstract

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. 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 <100 000 copies/mL, 25.0% for a VL of ≥100 000 copies/mL and <500 000 copies/mL and 53.8% for a VL of ≥500 000 copies/mL (PTREND = 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
Pages (from-to)1056-1062
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016

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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., ... Couffin-Cadiergues, S. (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. https://doi.org/10.1093/jac/dkv427