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 Allavena & 224 others Brigitte 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

14 Citations (Scopus)

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

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Tenofovir
Integrases
Ritonavir
Viral Load
Mutation
Peptide Hydrolases
RNA-Directed DNA Polymerase
Reverse Transcriptase Inhibitors
Mutation Rate
Drug Resistance
Genes
Darunavir
Emtricitabine
Raltegravir Potassium
Nucleotides

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 4, dkv427, 01.04.2016, p. 1056-1062.

Research output: Contribution to journalArticle

Lambert-Niclot, S, George, EC, Pozniak, A, White, E, Schwimmer, C, Jessen, H, Johnson, M, Dunn, D, Perno, CF, Clotet, B, Plettenberg, A, Blaxhult, A, Palmisano, L, Wittkop, L, Calvez, V, Marcelin, AG, Raffi, F, Dedes, N, Chěne, G, Allavena, C, Autran, B, Antinori, A, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Babiker, AG, Boffito, M, Pillay, D, Pozniak, A, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Richert, L, Wallet, C, Raffi, F, Diallo, A, Molina, JM, Saillard, J, Moecklinghoff, C, Stellbrink, HJ, Van Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, EC, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, BY, Goebel, F, Marcotullio, S, Kaur, N, Sasieni, P, Spencer-Drake, C, Peto, T, Miller, V, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Paraina, F, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, BG, Jakobsen, ML, Jansson, PO, Jensen, K, Joensen, ZM, Larsen, EM, Pahl, C, Pearson, M, Nielsen, BR, Reilev, SS, Christ, I, Lathouwers, D, Manting, C, Mendy, BY, Metro, A, Couffin-Cadiergues, S, Knellwolf, AL, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, De Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cabie, A, Cheret, A, Dupon, M, Ghosn, J, Girard, PM, Goujard, C, Lévy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Reynes, J, Tattevin, P, Ragnaud, JM, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fätkenheuer, G, Hoffmann, C, Jessen, H, Rockstroh, J, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, GL, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, ADA, Di Perri, G, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Van Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento-Castro, R, Garcia, JG, Aldeguer, JL, Clotet, B, Domingo, P, Gatell, JM, Knobel, H, Marquez, M, Miralles, MP, Portilla, J, Soriano, V, Tellez, MJ, Thalme, A, Blaxhult, A, Gisslen, M, Winston, A, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Williams, I, Boyd, MA, Møller, NF, Larsen, EFM, Piroth, L, Le Moing, V, Wit, FWNM, Kowalska, J, Berenguer, J, Moreno, S, Müller, NJ, Török, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, AG, Perno, CF, White, E, Ammassari, A, Stoehr, W, Schmidt, RE, Odermarsky, M, Smith, C, Thiébaut, R, De La Serna, JIB, Castagna, A, Furrer, HJ, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny-Anne, A, West, B, Amieva, H, Codina, JML, Braggion, M & 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, vol. 71, no. 4, dkv427, pp. 1056-1062. https://doi.org/10.1093/jac/dkv427
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, Nikos ; Chěne, Geneviève ; Allavena, Clotilde ; Autran, Brigitte ; Antinori, Andrea ; Bucciardini, Raffaella ; Vella, Stefano ; Horban, Andrzej ; Arribas, Jose ; Babiker, Abdel G. ; Boffito, Marta ; Pillay, Deenan ; Pozniak, Anton ; Franquet, Xavier ; Schwarze, Siegfried ; Grarup, Jesper ; Fischer, Aurélie ; Richert, Laura ; Wallet, Cédrick ; Raffi, François ; Diallo, Alpha ; Molina, Jean Michel ; Saillard, Juliette ; Moecklinghoff, Christiane ; Stellbrink, Hans Jürgen ; Van Leeuwen, Remko ; Gatell, Jose ; Sandstrom, Eric ; Flepp, Markus ; Ewings, Fiona ; George, Elizabeth C. ; Hudson, Fleur ; Pearce, Gillian ; Quercia, Romina ; Rogatto, Felipe ; Leavitt, Randi ; Nguyen, Bach Yen ; Goebel, Frank ; Marcotullio, Simone ; Kaur, Navrup ; Sasieni, Peter ; Spencer-Drake, Christina ; Peto, Tim ; Miller, Veronica ; Arnault, Fabien ; Boucherie, Céline ; Jean, Delphine ; Paniego, Virginie ; Paraina, Felasoa ; Rouch, Elodie ; Schwimmer, Christine ; Soussi, Malika ; Taieb, Audrey ; Termote, Monique ; Touzeau, Guillaume ; Cursley, Adam ; Dodds, Wendy ; Hoppe, Anne ; Kummeling, Ischa ; Pacciarini, Filippo ; Paton, Nick ; Russell, Charlotte ; Taylor, Kay ; Ward, Denise ; Aagaard, Bitten ; Eid, Marius ; Gey, Daniela ; Jensen, Birgitte Gram ; Jakobsen, Marie Louise ; Jansson, Per O. ; Jensen, Karoline ; Joensen, Zillah Maria ; Larsen, Ellen Moseholm ; Pahl, Christiane ; Pearson, Mary ; Nielsen, Birgit Riis ; Reilev, Søren Stentoft ; Christ, Ilse ; Lathouwers, Desiree ; Manting, Corry ; Mendy, Bienvenu Yves ; Metro, Annie ; Couffin-Cadiergues, Sandrine ; Knellwolf, Anne Laure ; Palmisiano, Lucia ; Aznar, Esther ; Barea, Cristina ; Cotarelo, Manuel ; Esteban, Herminia ; Girbau, Iciar ; Moyano, Beatriz ; Ramirez, Miriam ; Saiz, Carmen ; Sanchez, Isabel ; Yllescas, Maria ; Binelli, Andrea ; Colasanti, Valentina ; Massella, Maurizio ; Anagnostou, Olga ; Gioukari, Vicky ; Touloumi, Giota ; Schmied, Brigitte ; Rieger, Armin ; Vetter, Norbert ; De Wit, Stephane ; Florence, Eric ; Vandekerckhove, Linos ; Gerstoft, Jan ; Mathiesen, Lars ; Katlama, Christine ; Cabie, Andre ; Cheret, Antoine ; Dupon, Michel ; Ghosn, Jade ; Girard, Pierre Marie ; Goujard, Cécile ; Lévy, Yves ; Morlat, Philippe ; Neau, Didier ; Obadia, Martine ; Perre, Philippe ; Reynes, Jacques ; Tattevin, Pierre ; Ragnaud, Jean Marie ; Weiss, Laurence ; Yazdan, Yazdanpanah ; Yeni, Patrick ; Zucman, David ; Behrens, Georg ; Esser, Stefan ; Fätkenheuer, Gerd ; Hoffmann, Christian ; Jessen, Heiko ; Rockstroh, Jürgen ; Schmidt, Reinhold ; Stephan, Christoph ; Unger, Stefan ; Hatzakis, Angelos ; Daikos, George L. ; Papadopoulos, Antonios ; Skoutelis, Athamasios ; Banhegyi, Denes ; Mallon, Paddy ; Mulcahy, Fiona ; Andreoni, Massimo ; Bonora, Stefano ; Castelli, Francesco ; Monforte, Antonella D Arminio ; Di Perri, Giovanni ; Galli, Massimo ; Lazzarin, Adriano ; Mazzotta, Francesco ; Carlo, Torti ; Vullo, Vincenzo ; Prins, Jan ; Richter, Clemens ; Verhagen, Dominique ; Van Eeden, Arne ; Doroana, Manuela ; Antunes, Francisco ; Maltez, Fernando ; Sarmento-Castro, Rui ; Garcia, Juan Gonzalez ; Aldeguer, José López ; Clotet, Bonaventura ; Domingo, Pere ; Gatell, Jose M. ; Knobel, Hernando ; Marquez, Manuel ; Miralles, Martin Pilar ; Portilla, Joaquin ; Soriano, Vicente ; Tellez, Maria Jesus ; Thalme, Anders ; Blaxhult, Anders ; Gisslen, Magnus ; Winston, Alan ; Fox, Julie ; Gompels, Mark ; Herieka, Elbushra ; Johnson, Margaret ; Leen, Clifford ; Teague, Alastair ; Williams, Ian ; Boyd, Mark Alastair ; Møller, Nina Friis ; Larsen, Ellen Frøsig Moseholm ; Piroth, Lionel ; Le Moing, Vincent ; Wit, Ferdinand W N M ; Kowalska, Justyna ; Berenguer, Juan ; Moreno, Santiago ; Müller, Nicolas J. ; Török, Estée ; Post, Frank ; Angus, Brian ; Calvez, Vincent ; Boucher, Charles ; Collins, Simon ; Dunn, David ; Lambert, Sidonie ; Marcelin, Anne Geneviève ; Perno, Carlo Federico ; White, Ellen ; Ammassari, Adriana ; Stoehr, Wolgang ; Schmidt, Reinhold Ernst ; Odermarsky, Michal ; Smith, Colette ; Thiébaut, Rodolphe ; De La Serna, Jose Ignacio Bernardino ; Castagna, Antonella ; Furrer, Hans Jackob ; Mocroft, Amanda ; Reiss, Peter ; Fragola, Vincenzo ; Lauriola, Marco ; Murri, Rita ; Nieuwkerk, Pythia ; Spire, Bruno ; Volny-Anne, Alain ; West, Brian ; Amieva, Hélène ; Codina, Josep Maria Llibre ; Braggion, Marco ; Focá, Emanuele. / 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. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 4. pp. 1056-1062.
@article{37e3fc6712594e69a174e66015ea3e21,
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",
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{\%}.",
author = "S. Lambert-Niclot and George, {E. C.} and A. Pozniak and E. White and C. Schwimmer and H. Jessen and M. Johnson and D. Dunn and Perno, {C. F.} and B. Clotet and A. Plettenberg and A. Blaxhult and L. Palmisano and L. Wittkop and V. Calvez and Marcelin, {A. G.} and F. Raffi and Nikos Dedes and Genevi{\`e}ve Chěne and Clotilde Allavena and Brigitte Autran and Andrea Antinori and Raffaella Bucciardini and Stefano Vella and Andrzej Horban and Jose Arribas and Babiker, {Abdel G.} and Marta Boffito and Deenan Pillay and Anton Pozniak and Xavier Franquet and Siegfried Schwarze and Jesper Grarup and Aur{\'e}lie Fischer and Laura Richert and C{\'e}drick Wallet and Fran{\cc}ois Raffi and Alpha Diallo and Molina, {Jean Michel} and Juliette Saillard and Christiane Moecklinghoff and Stellbrink, {Hans J{\"u}rgen} and {Van Leeuwen}, Remko and Jose Gatell and Eric Sandstrom and Markus Flepp and Fiona Ewings and George, {Elizabeth C.} and Fleur Hudson and Gillian Pearce and Romina Quercia and Felipe Rogatto and Randi Leavitt and Nguyen, {Bach Yen} and Frank Goebel and Simone Marcotullio and Navrup Kaur and Peter Sasieni and Christina Spencer-Drake and Tim Peto and Veronica Miller and Fabien Arnault and C{\'e}line Boucherie and Delphine Jean and Virginie Paniego and Felasoa Paraina and Elodie Rouch and Christine Schwimmer and Malika Soussi and Audrey Taieb and Monique Termote and Guillaume Touzeau and Adam Cursley and Wendy Dodds and Anne Hoppe and Ischa Kummeling and Filippo Pacciarini and Nick Paton and Charlotte Russell and Kay Taylor and Denise Ward and Bitten Aagaard and Marius Eid and Daniela Gey and Jensen, {Birgitte Gram} and Jakobsen, {Marie Louise} and Jansson, {Per O.} and Karoline Jensen and Joensen, {Zillah Maria} and Larsen, {Ellen Moseholm} and Christiane Pahl and Mary Pearson and Nielsen, {Birgit Riis} and Reilev, {S{\o}ren Stentoft} and Ilse Christ and Desiree Lathouwers and Corry Manting and Mendy, {Bienvenu Yves} and Annie Metro and Sandrine Couffin-Cadiergues and Knellwolf, {Anne Laure} and Lucia Palmisiano and Esther Aznar and Cristina Barea and Manuel Cotarelo and Herminia Esteban and Iciar Girbau and Beatriz Moyano and Miriam Ramirez and Carmen Saiz and Isabel Sanchez and Maria Yllescas and Andrea Binelli and Valentina Colasanti and Maurizio Massella and Olga Anagnostou and Vicky Gioukari and Giota Touloumi and Brigitte Schmied and Armin Rieger and Norbert Vetter and {De Wit}, Stephane and Eric Florence and Linos Vandekerckhove and Jan Gerstoft and Lars Mathiesen and Christine Katlama and Andre Cabie and Antoine Cheret and Michel Dupon and Jade Ghosn and Girard, {Pierre Marie} and C{\'e}cile Goujard and Yves L{\'e}vy and Philippe Morlat and Didier Neau and Martine Obadia and Philippe Perre and Jacques Reynes and Pierre Tattevin and Ragnaud, {Jean Marie} and Laurence Weiss and Yazdanpanah Yazdan and Patrick Yeni and David Zucman and Georg Behrens and Stefan Esser and Gerd F{\"a}tkenheuer and Christian Hoffmann and Heiko Jessen and J{\"u}rgen Rockstroh and Reinhold Schmidt and Christoph Stephan and Stefan Unger and Angelos Hatzakis and Daikos, {George L.} and Antonios Papadopoulos and Athamasios Skoutelis and Denes Banhegyi and Paddy Mallon and Fiona Mulcahy and Massimo Andreoni and Stefano Bonora and Francesco Castelli and Monforte, {Antonella D Arminio} and {Di Perri}, Giovanni and Massimo Galli and Adriano Lazzarin and Francesco Mazzotta and Torti Carlo and Vincenzo Vullo and Jan Prins and Clemens Richter and Dominique Verhagen and {Van Eeden}, Arne and Manuela Doroana and Francisco Antunes and Fernando Maltez and Rui Sarmento-Castro and Garcia, {Juan Gonzalez} and Aldeguer, {Jos{\'e} L{\'o}pez} and Bonaventura Clotet and Pere Domingo and Gatell, {Jose M.} and Hernando Knobel and Manuel Marquez and Miralles, {Martin Pilar} and Joaquin Portilla and Vicente Soriano and Tellez, {Maria Jesus} and Anders Thalme and Anders Blaxhult and Magnus Gisslen and Alan Winston and Julie Fox and Mark Gompels and Elbushra Herieka and Margaret Johnson and Clifford Leen and Alastair Teague and Ian Williams and Boyd, {Mark Alastair} and M{\o}ller, {Nina Friis} and Larsen, {Ellen Fr{\o}sig Moseholm} and Lionel Piroth and {Le Moing}, Vincent and Wit, {Ferdinand W N M} and Justyna Kowalska and Juan Berenguer and Santiago Moreno and M{\"u}ller, {Nicolas J.} and Est{\'e}e T{\"o}r{\"o}k and Frank Post and Brian Angus and Vincent Calvez and Charles Boucher and Simon Collins and David Dunn and Sidonie Lambert and Marcelin, {Anne Genevi{\`e}ve} and Perno, {Carlo Federico} and Ellen White and Adriana Ammassari and Wolgang Stoehr and Schmidt, {Reinhold Ernst} and Michal Odermarsky and Colette Smith and Rodolphe Thi{\'e}baut and {De La Serna}, {Jose Ignacio Bernardino} and Antonella Castagna and Furrer, {Hans Jackob} and Amanda Mocroft and Peter Reiss and Vincenzo Fragola and Marco Lauriola and Rita Murri and Pythia Nieuwkerk and Bruno Spire and Alain Volny-Anne and Brian West and H{\'e}l{\`e}ne Amieva and Codina, {Josep Maria Llibre} and Marco Braggion and Emanuele Foc{\'a}",
year = "2016",
month = "4",
day = "1",
doi = "10.1093/jac/dkv427",
language = "English",
volume = "71",
pages = "1056--1062",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial

T2 - Raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

AU - Lambert-Niclot, S.

AU - George, E. C.

AU - Pozniak, A.

AU - White, E.

AU - Schwimmer, C.

AU - Jessen, H.

AU - Johnson, M.

AU - Dunn, D.

AU - Perno, C. F.

AU - Clotet, B.

AU - Plettenberg, A.

AU - Blaxhult, A.

AU - Palmisano, L.

AU - Wittkop, L.

AU - Calvez, V.

AU - Marcelin, A. G.

AU - Raffi, F.

AU - Dedes, Nikos

AU - Chěne, Geneviève

AU - Allavena, Clotilde

AU - Autran, Brigitte

AU - Antinori, Andrea

AU - Bucciardini, Raffaella

AU - Vella, Stefano

AU - Horban, Andrzej

AU - Arribas, Jose

AU - Babiker, Abdel G.

AU - Boffito, Marta

AU - Pillay, Deenan

AU - Pozniak, Anton

AU - Franquet, Xavier

AU - Schwarze, Siegfried

AU - Grarup, Jesper

AU - Fischer, Aurélie

AU - Richert, Laura

AU - Wallet, Cédrick

AU - Raffi, François

AU - Diallo, Alpha

AU - Molina, Jean Michel

AU - Saillard, Juliette

AU - Moecklinghoff, Christiane

AU - Stellbrink, Hans Jürgen

AU - Van Leeuwen, Remko

AU - Gatell, Jose

AU - Sandstrom, Eric

AU - Flepp, Markus

AU - Ewings, Fiona

AU - George, Elizabeth C.

AU - Hudson, Fleur

AU - Pearce, Gillian

AU - Quercia, Romina

AU - Rogatto, Felipe

AU - Leavitt, Randi

AU - Nguyen, Bach Yen

AU - Goebel, Frank

AU - Marcotullio, Simone

AU - Kaur, Navrup

AU - Sasieni, Peter

AU - Spencer-Drake, Christina

AU - Peto, Tim

AU - Miller, Veronica

AU - Arnault, Fabien

AU - Boucherie, Céline

AU - Jean, Delphine

AU - Paniego, Virginie

AU - Paraina, Felasoa

AU - Rouch, Elodie

AU - Schwimmer, Christine

AU - Soussi, Malika

AU - Taieb, Audrey

AU - Termote, Monique

AU - Touzeau, Guillaume

AU - Cursley, Adam

AU - Dodds, Wendy

AU - Hoppe, Anne

AU - Kummeling, Ischa

AU - Pacciarini, Filippo

AU - Paton, Nick

AU - Russell, Charlotte

AU - Taylor, Kay

AU - Ward, Denise

AU - Aagaard, Bitten

AU - Eid, Marius

AU - Gey, Daniela

AU - Jensen, Birgitte Gram

AU - Jakobsen, Marie Louise

AU - Jansson, Per O.

AU - Jensen, Karoline

AU - Joensen, Zillah Maria

AU - Larsen, Ellen Moseholm

AU - Pahl, Christiane

AU - Pearson, Mary

AU - Nielsen, Birgit Riis

AU - Reilev, Søren Stentoft

AU - Christ, Ilse

AU - Lathouwers, Desiree

AU - Manting, Corry

AU - Mendy, Bienvenu Yves

AU - Metro, Annie

AU - Couffin-Cadiergues, Sandrine

AU - Knellwolf, Anne Laure

AU - Palmisiano, Lucia

AU - Aznar, Esther

AU - Barea, Cristina

AU - Cotarelo, Manuel

AU - Esteban, Herminia

AU - Girbau, Iciar

AU - Moyano, Beatriz

AU - Ramirez, Miriam

AU - Saiz, Carmen

AU - Sanchez, Isabel

AU - Yllescas, Maria

AU - Binelli, Andrea

AU - Colasanti, Valentina

AU - Massella, Maurizio

AU - Anagnostou, Olga

AU - Gioukari, Vicky

AU - Touloumi, Giota

AU - Schmied, Brigitte

AU - Rieger, Armin

AU - Vetter, Norbert

AU - De Wit, Stephane

AU - Florence, Eric

AU - Vandekerckhove, Linos

AU - Gerstoft, Jan

AU - Mathiesen, Lars

AU - Katlama, Christine

AU - Cabie, Andre

AU - Cheret, Antoine

AU - Dupon, Michel

AU - Ghosn, Jade

AU - Girard, Pierre Marie

AU - Goujard, Cécile

AU - Lévy, Yves

AU - Morlat, Philippe

AU - Neau, Didier

AU - Obadia, Martine

AU - Perre, Philippe

AU - Reynes, Jacques

AU - Tattevin, Pierre

AU - Ragnaud, Jean Marie

AU - Weiss, Laurence

AU - Yazdan, Yazdanpanah

AU - Yeni, Patrick

AU - Zucman, David

AU - Behrens, Georg

AU - Esser, Stefan

AU - Fätkenheuer, Gerd

AU - Hoffmann, Christian

AU - Jessen, Heiko

AU - Rockstroh, Jürgen

AU - Schmidt, Reinhold

AU - Stephan, Christoph

AU - Unger, Stefan

AU - Hatzakis, Angelos

AU - Daikos, George L.

AU - Papadopoulos, Antonios

AU - Skoutelis, Athamasios

AU - Banhegyi, Denes

AU - Mallon, Paddy

AU - Mulcahy, Fiona

AU - Andreoni, Massimo

AU - Bonora, Stefano

AU - Castelli, Francesco

AU - Monforte, Antonella D Arminio

AU - Di Perri, Giovanni

AU - Galli, Massimo

AU - Lazzarin, Adriano

AU - Mazzotta, Francesco

AU - Carlo, Torti

AU - Vullo, Vincenzo

AU - Prins, Jan

AU - Richter, Clemens

AU - Verhagen, Dominique

AU - Van Eeden, Arne

AU - Doroana, Manuela

AU - Antunes, Francisco

AU - Maltez, Fernando

AU - Sarmento-Castro, Rui

AU - Garcia, Juan Gonzalez

AU - Aldeguer, José López

AU - Clotet, Bonaventura

AU - Domingo, Pere

AU - Gatell, Jose M.

AU - Knobel, Hernando

AU - Marquez, Manuel

AU - Miralles, Martin Pilar

AU - Portilla, Joaquin

AU - Soriano, Vicente

AU - Tellez, Maria Jesus

AU - Thalme, Anders

AU - Blaxhult, Anders

AU - Gisslen, Magnus

AU - Winston, Alan

AU - Fox, Julie

AU - Gompels, Mark

AU - Herieka, Elbushra

AU - Johnson, Margaret

AU - Leen, Clifford

AU - Teague, Alastair

AU - Williams, Ian

AU - Boyd, Mark Alastair

AU - Møller, Nina Friis

AU - Larsen, Ellen Frøsig Moseholm

AU - Piroth, Lionel

AU - Le Moing, Vincent

AU - Wit, Ferdinand W N M

AU - Kowalska, Justyna

AU - Berenguer, Juan

AU - Moreno, Santiago

AU - Müller, Nicolas J.

AU - Török, Estée

AU - Post, Frank

AU - Angus, Brian

AU - Calvez, Vincent

AU - Boucher, Charles

AU - Collins, Simon

AU - Dunn, David

AU - Lambert, Sidonie

AU - Marcelin, Anne Geneviève

AU - Perno, Carlo Federico

AU - White, Ellen

AU - Ammassari, Adriana

AU - Stoehr, Wolgang

AU - Schmidt, Reinhold Ernst

AU - Odermarsky, Michal

AU - Smith, Colette

AU - Thiébaut, Rodolphe

AU - De La Serna, Jose Ignacio Bernardino

AU - Castagna, Antonella

AU - Furrer, Hans Jackob

AU - Mocroft, Amanda

AU - Reiss, Peter

AU - Fragola, Vincenzo

AU - Lauriola, Marco

AU - Murri, Rita

AU - Nieuwkerk, Pythia

AU - Spire, Bruno

AU - Volny-Anne, Alain

AU - West, Brian

AU - Amieva, Hélène

AU - Codina, Josep Maria Llibre

AU - Braggion, Marco

AU - Focá, Emanuele

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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%.

AB - 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%.

UR - http://www.scopus.com/inward/record.url?scp=84964317330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964317330&partnerID=8YFLogxK

U2 - 10.1093/jac/dkv427

DO - 10.1093/jac/dkv427

M3 - Article

VL - 71

SP - 1056

EP - 1062

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 4

M1 - dkv427

ER -