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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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published
subject
keywords
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
in
Journal of Antimicrobial Chemotherapy
volume
71
issue
4
article number
dkv427
pages
7 pages
publisher
Oxford University Press
external identifiers
  • scopus:84964317330
  • pmid:26702926
ISSN
1460-2091
DOI
10.1093/jac/dkv427
language
English
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yes
id
be6b69eb-bc4a-409c-8937-f903a6afa5a3
date added to LUP
2016-05-04 05:23:11
date last changed
2022-04-16 08:58:02
@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>}},
  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 Odermarsky, Michal}},
  issn         = {{1460-2091}},
  keywords     = {{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}},
  doi          = {{10.1093/jac/dkv427}},
  volume       = {{71}},
  year         = {{2016}},
}