TY - JOUR
T1 - 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
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 - AUTHOR GROUP
AU - Dedes, Nikos
AU - Chêne, Geneviève
AU - Richert, Laura
AU - Allavena, Clotilde
AU - Raffi, François
AU - Autran, Brigitte
AU - Antinori, Andrea
AU - Bucciardini, Raff Aella
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 - Wallet, Cédrick
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 - Prins, Jan
AU - Wit, Ferdinand W. N. M.
AU - Reiss, Peter
AU - Nieuwkerk, Pythia
PY - 2016
Y1 - 2016
N2 - 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). 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. 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 <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. 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 - 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). 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. 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 <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. 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%
U2 - https://doi.org/10.1093/jac/dkv427
DO - https://doi.org/10.1093/jac/dkv427
M3 - Article
C2 - 26702926
SN - 0305-7453
VL - 71
SP - 1056
EP - 1062
JO - Journal of antimicrobial chemotherapy
JF - Journal of antimicrobial chemotherapy
IS - 4
ER -