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

on behalf of the NEAT 001/ANRS 143 Study Group

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
Emtricitabine
Darunavir
Raltegravir Potassium
Nucleotides

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. / on behalf of the NEAT 001/ANRS 143 Study Group.

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

Research output: Contribution to journalArticle

@article{8ce2a9859cb94f5dbcc8f1692f4273e3,
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 = "{on behalf of the NEAT 001/ANRS 143 Study Group} and 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 D. B{\'a}nhegyi",
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month = "4",
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doi = "10.1093/jac/dkv427",
language = "English",
volume = "71",
pages = "1056--1062",
journal = "Journal of Antimicrobial Chemotherapy",
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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 - on behalf of the NEAT 001/ANRS 143 Study Group

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 - Bánhegyi, D.

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%.

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DO - 10.1093/jac/dkv427

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JF - Journal of Antimicrobial Chemotherapy

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