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
Articolo
Data di Pubblicazione:
2016
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 <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.
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%.
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 <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.
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%.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Treatment Failure; Treatment Outcome; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Viral Load
Elenco autori:
Lambert-Niclot, S.; George, E. C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, A.; Blaxhult, A.; Palmisano, L.; Wittkop, L.; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, N.; Chene, G.; Allavena, C.; Autran, B.; Antinori, A.; Bucciardini, R.; Vella, S.; Horban, A.; Arribas, J.; Babiker, A. G.; Boffito, M.; Pillay, D.; Pozniak, A.; Franquet, X.; Schwarze, S.; Grarup, J.; Fischer, A.; Richert, L.; Wallet, C.; Raffi, F.; Diallo, A.; Molina, J. -M.; Saillard, J.; Moecklinghoff, C.; Stellbrink, H. -J.; Van Leeuwen, R.; Gatell, J.; Sandstrom, E.; Flepp, M.; Ewings, F.; George, E. C.; Hudson, F.; Pearce, G.; Quercia, R.; Rogatto, F.; Leavitt, R.; Nguyen, B. -Y.; Goebel, F.; Marcotullio, S.; Kaur, N.; Sasieni, P.; Spencer-Drake, C.; Peto, T.; Miller, V.; Arnault, F.; Boucherie, C.; Jean, D.; Paniego, V.; Paraina, F.; Rouch, E.; Schwimmer, C.; Soussi, M.; Taieb, A.; Termote, M.; Touzeau, G.; Cursley, A.; Dodds, W.; Hoppe, A.; Kummeling, I.; Pacciarini, F.; Paton, N.; Russell, C.; Taylor, K.; Ward, D.; Aagaard, B.; Eid, M.; Gey, D.; Jensen, B. G.; Jakobsen, M. -L.; Jansson, P. O.; Jensen, K.; Joensen, Z. M.; Larsen, E. M.; Pahl, C.; Pearson, M.; Nielsen, B. R.; Reilev, S. S.; Christ, I.; Lathouwers, D.; Manting, C.; Mendy, B. Y.; Metro, A.; Couffin-Cadiergues, S.; Knellwolf, A. -L.; Palmisiano, L.; Aznar, E.; Barea, C.; Cotarelo, M.; Esteban, H.; Girbau, I.; Moyano, B.; Ramirez, M.; Saiz, C.; Sanchez, I.; Yllescas, M.; Binelli, A.; Colasanti, V.; Massella, M.; Anagnostou, O.; Gioukari, V.; Touloumi, G.; Schmied, B.; Rieger, A.; Vetter, N.; De Wit, S.; Florence, E.; Vandekerckhove, L.; Gerstoft, J.; Mathiesen, L.; Katlama, C.; Cabie, A.; Cheret, A.; Dupon, M.; Ghosn, J.; Girard, P. -M.; Goujard, C.; Levy, Y.; Morlat, P.; Neau, D.; Obadia, M.; Perre, P.; Reynes, J.; Tattevin, P.; Ragnaud, J. M.; Weiss, L.; Yazdan, Y.; Yeni, P.; Zucman, D.; Behrens, G.; Esser, S.; Fatkenheuer, G.; Hoffmann, C.; Jessen, H.; Rockstroh, J.; Schmidt, R.; Stephan, C.; Unger, S.; Hatzakis, A.; Daikos, G. L.; Papadopoulos, A.; Skoutelis, A.; Banhegyi, D.; Mallon, P.; Mulcahy, F.; Andreoni, M.; Bonora, S.; Castelli, F.; Monforte, A. D.; Di Perri, G.; Galli, M.; Lazzarin, A.; Mazzotta, F.; Carlo, T.; Vullo, V.; Prins, J.; Richter, C.; Verhagen, D.; Van Eeden, A.; Doroana, M.; Antunes, F.; Maltez, F.; Sarmento-Castro, R.; Garcia, J. G.; Aldeguer, J. L.; Clotet, B.; Domingo, P.; Gatell, J. M.; Knobel, H.; Marquez, M.; Miralles, M. P.; Portilla, J.; Soriano, V.; Tellez, M. -J.; Thalme, A.; Blaxhult, A.; Gisslen, M.; Winston, A.; Fox, J.; Gompels, M.; Herieka, E.; Johnson, M.; Leen, C.; Teague, A.; Williams, I.; Boyd, M. A.; Moller, N. F.; Larsen, E. F. M.; Piroth, L.; Le Moing, V.; Wit, F. W. N. M.; Kowalska, J.; Berenguer, J.; Moreno, S.; Muller, N. J.; Torok, E.; Post, F.; Angus, B.; Calvez, V.; Boucher, C.; Collins, S.; Dunn, D.; Lambert, S.; Marcelin, A. -G.; White, E.; Ammassari, A.; Stoehr, W.; Schmidt, R. E.; Odermarsky, M.; Smith, C.; Thiebaut, R.; De La Serna, J. I. B.; Castagna, A.; Furrer, H. -J.; Mocroft, A.; Reiss, P.; Fragola, V.; Lauriola, M.; Murri, R.; Nieuwkerk, P.; Spire, B.; Volny-Anne, A.; West, B.; Amieva, H.; Codina, J. M. L.; Braggion, M.; Foca, E.
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