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 language | English |
|---|---|
| Article number | dkv427 |
| Pages (from-to) | 1056-1062 |
| Number of pages | 7 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 71 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2016 |
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
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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, Sidonie; George, E. C.; Pozniak, A.; White, E.; Schwimmer, Christine; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, Andreas; Blaxhult, A.; Palmisano, Lucia; Wittkop, Linda; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, N.; Chene, Genevieve; Allavena, Clotilde; Autran, Brigitte; Antinori, Andrea; Bucciardini, R.; Vella, S.; Horban, A.; Arribas, J.; Babiker, Abdel; Boffito, Marta; Pillay, Deenan; Pozniak, A.; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurélie; Richert, L.; Wallet, Cédrick; Raffi, F.; Diallo, Alpha; Molina, Jean Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, H. J.; Van Leeuwen, Remko; Gatell, J. M.; Sandström, E.; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, F.; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, T. E A; 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 Olof; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren; 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, B.; Rieger, Armin; Vetter, N.; De Wit, Stéphane; Florence, E.; Vandekerckhove, L.; Gerstoft, J.; Mathiesen, L.; Katlama, Christine; Cabié, A.; Cheret, Antoine; Dupon, M.; Ghosn, Jade; Girard, Pierre Marie; Goujard, C.; Levy, Y.; Morlat, P.; Neau, D.; Obadia, Martine; Perre, Philippe; Reynes, Jacques; Tattevin, Pierre; Ragnaud, J. M.; Weiss, L.; Yazdan, Yazdanpanah; Yeni, P.; Zucman, David; Behrens, G.; Esser, S.; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, J.; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, A.; Daikos, G. L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Bánhegyi, Dénes; Mallon, Patrick W.; Mulcahy, F.; Andreoni, M.; Bonora, S.; Castelli, F.; Monforte, Antonella D.; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Mazzotta, F.; Carlo, Torti; Vullo, Vincenzo; Prins, J. M.; Richter, C.; Verhagen, Dominique; van Eeden, A.; Doroana, M.; Antunes, Francisco; Maltez, F.; Sarmento-Castro, Rui; Garcia, Juan Gonzalez; Aldeguer, José López; Clotet, Bonaventura; Domingo, P.; Gatell, Jose M.; Knobel, H.; Marquez, Manuel; Miralles, Martin Pilar; Portilla, Joaquín; Soriano, Vicente; Tellez, Maria Jesus; Thalme, A.; Blaxhult, A.; Gisslén, Magnus; Winston, Alan; Fox, Julie; Gompels, M. M.; Herieka, Elbushra; Johnson, Margaret; Leen, C.; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Moller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Piroth, Lionel; Le Moing, Vincent; Wit, Ferdinand; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, N.; Török, Estée; Post, Frank A.; Angus, Brian; Calvez, V.; Boucher, C. A B; Collins, Simon; Dunn, D.; Lambert, Sidonie; Marcelin, Anne Geneviève; Perno, Carlo Federico; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiebaut, Rodolphe; De La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans Jackob; Mocroft, Amanda; Reiss, Peter; Fragola, V.; Lauriola, Marco; Murri, R.; Nieuwkerk, Pythia; Spire, B.; Volny-Anne, Alain; West, Brian; Amieva, H.; Codina, Josep Maria Llibre; Braggion, Marco; Focà, Emanuele.
In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 4, dkv427, 01.04.2016, p. 1056-1062.Research output: Contribution to journal › Article › peer-review
}
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, Sidonie
AU - George, E. C.
AU - Pozniak, A.
AU - White, E.
AU - Schwimmer, Christine
AU - Jessen, H.
AU - Johnson, M.
AU - Dunn, D.
AU - Perno, C. F.
AU - Clotet, B.
AU - Plettenberg, Andreas
AU - Blaxhult, A.
AU - Palmisano, Lucia
AU - Wittkop, Linda
AU - Calvez, V.
AU - Marcelin, A. G.
AU - Raffi, F.
AU - Dedes, N.
AU - Chene, Genevieve
AU - Allavena, Clotilde
AU - Autran, Brigitte
AU - Antinori, Andrea
AU - Bucciardini, R.
AU - Vella, S.
AU - Horban, A.
AU - Arribas, J.
AU - Babiker, Abdel
AU - Boffito, Marta
AU - Pillay, Deenan
AU - Pozniak, A.
AU - Franquet, Xavier
AU - Schwarze, Siegfried
AU - Grarup, Jesper
AU - Fischer, Aurélie
AU - Richert, L.
AU - Wallet, Cédrick
AU - Raffi, F.
AU - Diallo, Alpha
AU - Molina, Jean Michel
AU - Saillard, Juliette
AU - Moecklinghoff, Christiane
AU - Stellbrink, H. J.
AU - Van Leeuwen, Remko
AU - Gatell, J. M.
AU - Sandström, E.
AU - Flepp, Markus
AU - Ewings, Fiona
AU - George, Elizabeth C.
AU - Hudson, F.
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, T. E A
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 Olof
AU - Jensen, Karoline
AU - Joensen, Zillah Maria
AU - Larsen, Ellen Moseholm
AU - Pahl, Christiane
AU - Pearson, Mary
AU - Nielsen, Birgit Riis
AU - Reilev, Søren
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, B.
AU - Rieger, Armin
AU - Vetter, N.
AU - De Wit, Stéphane
AU - Florence, E.
AU - Vandekerckhove, L.
AU - Gerstoft, J.
AU - Mathiesen, L.
AU - Katlama, Christine
AU - Cabié, A.
AU - Cheret, Antoine
AU - Dupon, M.
AU - Ghosn, Jade
AU - Girard, Pierre Marie
AU - Goujard, C.
AU - Levy, Y.
AU - Morlat, P.
AU - Neau, D.
AU - Obadia, Martine
AU - Perre, Philippe
AU - Reynes, Jacques
AU - Tattevin, Pierre
AU - Ragnaud, J. M.
AU - Weiss, L.
AU - Yazdan, Yazdanpanah
AU - Yeni, P.
AU - Zucman, David
AU - Behrens, G.
AU - Esser, S.
AU - Fätkenheuer, Gerd
AU - Hoffmann, Christian
AU - Jessen, Heiko
AU - Rockstroh, J.
AU - Schmidt, Reinhold
AU - Stephan, Christoph
AU - Unger, Stefan
AU - Hatzakis, A.
AU - Daikos, G. L.
AU - Papadopoulos, Antonios
AU - Skoutelis, Athamasios
AU - Bánhegyi, Dénes
AU - Mallon, Patrick W.
AU - Mulcahy, F.
AU - Andreoni, M.
AU - Bonora, S.
AU - Castelli, F.
AU - Monforte, Antonella D.
AU - Di Perri, Giovanni
AU - Galli, Massimo
AU - Lazzarin, Adriano
AU - Mazzotta, F.
AU - Carlo, Torti
AU - Vullo, Vincenzo
AU - Prins, J. M.
AU - Richter, C.
AU - Verhagen, Dominique
AU - van Eeden, A.
AU - Doroana, M.
AU - Antunes, Francisco
AU - Maltez, F.
AU - Sarmento-Castro, Rui
AU - Garcia, Juan Gonzalez
AU - Aldeguer, José López
AU - Clotet, Bonaventura
AU - Domingo, P.
AU - Gatell, Jose M.
AU - Knobel, H.
AU - Marquez, Manuel
AU - Miralles, Martin Pilar
AU - Portilla, Joaquín
AU - Soriano, Vicente
AU - Tellez, Maria Jesus
AU - Thalme, A.
AU - Blaxhult, A.
AU - Gisslén, Magnus
AU - Winston, Alan
AU - Fox, Julie
AU - Gompels, M. M.
AU - Herieka, Elbushra
AU - Johnson, Margaret
AU - Leen, C.
AU - Teague, Alastair
AU - Williams, Ian
AU - Boyd, Mark Alastair
AU - Moller, Nina Friis
AU - Larsen, Ellen Frøsig Moseholm
AU - Piroth, Lionel
AU - Le Moing, Vincent
AU - Wit, Ferdinand
AU - Kowalska, Justyna
AU - Berenguer, Juan
AU - Moreno, Santiago
AU - Müller, N.
AU - Török, Estée
AU - Post, Frank A.
AU - Angus, Brian
AU - Calvez, V.
AU - Boucher, C. A B
AU - Collins, Simon
AU - Dunn, D.
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 - Thiebaut, Rodolphe
AU - De La Serna, Jose Ignacio Bernardino
AU - Castagna, Antonella
AU - Furrer, Hans Jackob
AU - Mocroft, Amanda
AU - Reiss, Peter
AU - Fragola, V.
AU - Lauriola, Marco
AU - Murri, R.
AU - Nieuwkerk, Pythia
AU - Spire, B.
AU - Volny-Anne, Alain
AU - West, Brian
AU - Amieva, H.
AU - Codina, Josep Maria Llibre
AU - Braggion, Marco
AU - Focà, 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 -