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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

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Author

  • 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
  • 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
  • Michal Odermarsky
Show all

Summary, in English

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%.

Publishing year

2016-04-01

Language

English

Pages

1056-1062

Publication/Series

Journal of Antimicrobial Chemotherapy

Volume

71

Issue

4

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Infectious Medicine

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

Status

Published

Research group

  • Child and Family Health

ISBN/ISSN/Other

  • ISSN: 1460-2091