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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

Lambert-Niclot, S.; George, E.C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C.F. and Clotet, B., et al. (2016) In Journal of Antimicrobial Chemotherapy 71(4). p.1056-1062
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... (More)

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%.

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clinical trial, controlled clinical trial, controlled study, follow up, gene frequency, gene mutation, genetic predisposition, human, major clinical study, mutation, randomized controlled trial, virus load, darunavir, emtricitabine, integrase, nucleotide, proteinase, raltegravir, ritonavir, RNA directed DNA polymerase, tenofovir
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Journal of Antimicrobial Chemotherapy
volume
71
issue
4
pages
7 pages
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Oxford University Press
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  • scopus:84964317330
ISSN
1460-2091
DOI
10.1093/jac/dkv427
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English
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be6b69eb-bc4a-409c-8937-f903a6afa5a3
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2016-05-04 05:23:11
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@article{be6b69eb-bc4a-409c-8937-f903a6afa5a3,
  abstract     = {<p>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) &gt;50 copies/mL or any single VL &gt;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 &lt;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%.</p>},
  articleno    = {dkv427},
  author       = {Lambert-Niclot, S. and George, E.C. and Pozniak, A. and White, E. and Schwimmer, C. and Jessen, H. and Johnson, M. and Dunn, D. and Perno, C.F. and Clotet, B. and Plettenberg, A. and Blaxhult, A. and Palmisano, L. and Wittkop, L. and Calvez, V. and Marcelin, A.G. and Raffi, F. and Dedes, Nikos and Chěne, Geneviève and Allavena, Clotilde and Autran, Brigitte and Antinori, Andrea and Bucciardini , Raffaella and Vella, Stefano and Horban, Andrzej and Arribas, Jose and Babiker, Abdel G. and Boffito, Marta and Pillay, Deenan and Pozniak, Anton and Franquet, Xavier and Schwarze, Siegfried and Grarup, Jesper and Fischer, Aurélie and Richert, Laura and Wallet, Cédrick and Raffi, François and Diallo, Alpha and Molina, Jean-Michel and Saillard, Juliette and Moecklinghoff, Christiane and Stellbrink, Hans-Jürgen and Van Leeuwen, Remko and Gatell, Jose and Sandstrom, Eric and Flepp, Markus and Ewings, Fiona and George, Elizabeth C. and Hudson, Fleur and Pearce, Gillian and 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Annie and Couffin-Cadiergues, Sandrine and Knellwolf, Anne-Laure and Palmisiano, Lucia and Aznar, Esther and Barea, Cristina and Cotarelo, Manuel and Esteban, Herminia and Girbau, Iciar and Moyano, Beatriz and Ramirez, Miriam and Saiz, Carmen and Sanchez, Isabel and Yllescas, Maria and Binelli, Andrea and Colasanti, Valentina and Massella, Maurizio and Anagnostou, Olga and Gioukari, Vicky and Touloumi, Giota and Schmied, Brigitte and Rieger, Armin and Vetter, Norbert and De Wit, Stephane and Florence, Eric and Vandekerckhove, Linos and Gerstoft, Jan and Mathiesen, Lars and Katlama, Christine and Cabie, Andre and Cheret, Antoine and Dupon, Michel and Ghosn, Jade and Girard, Pierre-Marie and Goujard, Cécile and Lévy, Yves and Morlat, Philippe and Neau, Didier and Obadia, Martine and Perre, Philippe and Reynes, Jacques and Tattevin, Pierre and Ragnaud, Jean Marie and Weiss, Laurence and Yazdan, Yazdanpanah and Yeni, Patrick and Zucman, David and Behrens, Georg and Esser, Stefan and Fätkenheuer, Gerd and Hoffmann, Christian and Jessen, Heiko and Rockstroh, Jürgen and Schmidt, Reinhold and Stephan, Christoph and Unger, Stefan and Hatzakis, Angelos and Daikos, George L. and Papadopoulos, Antonios and Skoutelis, Athamasios and Banhegyi, Denes and Mallon, Paddy and Mulcahy, Fiona and Andreoni, Massimo and Bonora, Stefano and Castelli, Francesco and Monforte, Antonella D'Arminio and Di Perri, Giovanni and Galli, Massimo and Lazzarin, Adriano and Mazzotta, Francesco and Carlo, Torti and Vullo, Vincenzo and Prins, Jan and Richter, Clemens and Verhagen, Dominique and Van Eeden, Arne and Doroana, Manuela and Antunes, Francisco and Maltez, Fernando and Sarmento-Castro, Rui and Garcia, Juan Gonzalez and Aldeguer, José López and Clotet, Bonaventura and Domingo, Pere and Gatell, Jose M. and Knobel, Hernando and Marquez, Manuel and Miralles, Martin Pilar and Portilla, Joaquin and Soriano, Vicente and Tellez, Maria-Jesus and Thalme, Anders and Blaxhult, Anders and Gisslen, Magnus and Winston, Alan and Fox, Julie and Gompels, Mark and Herieka, Elbushra and Johnson, Margaret and Leen, Clifford and Teague, Alastair and Williams, Ian and Boyd, Mark Alastair and Møller, Nina Friis and Larsen, Ellen Frøsig Moseholm and Piroth, Lionel and Le Moing, Vincent and Wit, Ferdinand W.N.M. and Kowalska, Justyna and Berenguer, Juan and Moreno, Santiago and Müller, Nicolas J. and Török, Estée and Post, Frank and Angus, Brian and Calvez, Vincent and Boucher, Charles and Collins, Simon and Dunn, David and Lambert, Sidonie and Marcelin, Anne-Geneviève and Perno, Carlo Federico and White, Ellen and Ammassari, Adriana and Stoehr, Wolgang and Schmidt, Reinhold Ernst and Odermarsky, Michal and Smith, Colette and Thiébaut, Rodolphe and De La Serna, Jose Ignacio Bernardino and Castagna, Antonella and Furrer, Hans-Jackob and Mocroft, Amanda and Reiss, Peter and Fragola, Vincenzo and Lauriola, Marco and Murri, Rita and Nieuwkerk, Pythia and Spire, Bruno and Volny-Anne, Alain and West, Brian and Amieva, Hélène and Codina, Josep Maria Llibre and Braggion, Marco and Focá, Emanuele and , },
  issn         = {1460-2091},
  keyword      = {clinical trial,controlled clinical trial,controlled study,follow up,gene frequency,gene mutation,genetic predisposition,human,major clinical study,mutation,randomized controlled trial,virus load,darunavir,emtricitabine,integrase,nucleotide,proteinase,raltegravir,ritonavir,RNA directed DNA polymerase,tenofovir},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {1056--1062},
  publisher    = {Oxford University Press},
  series       = {Journal of Antimicrobial Chemotherapy},
  title        = {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},
  url          = {http://dx.doi.org/10.1093/jac/dkv427},
  volume       = {71},
  year         = {2016},
}