Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients. (3rd January 2015)

• Record Type: Journal Article
• Authors: Fourati, Slim; Charpentier, Charlotte; Amiel, Corinne; Morand-Joubert, Laurence; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Nicot, Florence; Rodallec, Audrey; Maillard, Anne; Mirand, Audrey; Jeulin, Hélène; Montès, Brigitte; Barin, Francis; Bettinger, Dominique; Le Guillou-Guillemette, Hélène; Vallet, Sophie; Signori-Schmuck, Anne; Descamps, Diane; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Genevieve; Lagier, E.; Roussel, C.; Le Guillou, H.; Alloui, C.; Bettinger, D.; Pallier, C.; Fleury, H.; Reigadas, S.; Bellecave, P.; Recordon-Pinson, P.; Payan, C.; Vallet, S.; Vabret, A.; Henquell, C.; Mirand, A.; Bouvier-Alias, M.; de Rougemont, A.; Dos Santos, G.; Morand, P.; Signori-Schmuck, A.; Bocket, L.; Rogez, S.; Andre, P.; Tardy, J. C.; Trabaud, M. A.; Tamalet, C.; Delamare, C.; Montes, B.; Schvoerer, E.; Ferre, V.; André-Garnier, E.; Cottalorda, J.; Guinard, J.; Guiguon, A.; Descamps, D.; Brun-Vézinet, F.; Charpentier, C.; Visseaux, B.; Peytavin, G.; Krivine, A.; Si-Mohamed, A.; Avettand-Fenoel, V.; Marcelin, A. G.; Calvez, V.; Lambert-Niclot, S.; Soulié, C.; Wirden, M.; Morand-Joubert, L.; Delaugerre, C.; Chaix, M. L.; Amiel, C.; Schneider, V.; Giraudeau, G.; Brodard, V.; Maillard, A.; Plantier, J. C.; Chaplain, C.; Bourlet, T.; Fafi-Kremer, S.; Stoll-Keller, F.; Schmitt, M. P.; Barth, H.; Yerly, S.; Poggi, C.; Izopet, J.; Raymond, S.; Barin, F.; Chaillon, A.; Marque-Juillet, S.; Roque-Afonso, A. M.; Haïm-Boukobza, S.; Flandre, P.; Grudé, M.; Assoumou, L.; Costagliola, D.; Allegre, T.; Schmit, J. L.; Chennebault, J. M.; Bouchaud, O.; Magy-Bertrand, N.; Delfraissy, J. F.; Dupon, M.; Morlat, P.; Neau, D.; Ansart, S.; Jaffuel, S.; Verdon, R.; Jacomet, C.; Lévy, Y.; Dominguez, S.; Chavanet, P.; Piroth, L.; Cabié, A.; Leclercq, P.; Ajana, F.; Cheret, A.; Weinbreck, P.; Cotte, L.; Poizot-Martin, I.; Ravaud, I.; Christian, B.; Truchetet, F.; Grandidier, M.; Reynes, J.; May, T.; Goehringer, F.; Raffi, F.; Dellamonica, P.; Prazuck, T.; Hocqueloux, L.; Yéni, P.; Landman, R.; Launay, O.; Weiss, L.; Viard, J. P.; Katlama, C.; Simon, A.; Girard, P.M.; Meynard, J. L.; Molina, J. M.; Pialoux, G.; Hoen, B.; Goeger-Sow, M. T.; Lamaury, I.; Beaucaire, G.; Jaussaud, R.; Rouger, C.; Michelet, C.; Borsa-Lebas, F.; Caron, F.; Khuong, M. A.; Lucht, F.; Rey, D.; Calmy, A.; Marchou, B.; Gras, G.; Greder-Belan, A.; Vittecoq, D.; Teicher, E.;
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 70:Number 5(2015:May)
• Page Start: 1507
• Page End: 1512
• Publication Date: 2015-01-03
• Subjects: integrase -- inhibitors -- mutations -- patterns; Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dku535
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). Patients and methods: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). Results: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure ( P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir ( P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes ( P = 0.004). Conclusions: This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.