1. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
- Author
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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, JC, Trabaud, MA, 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, AG, Calvez, V, Lambert-Niclot, S, Soulié, C, Wirden, M, Morand-Joubert, L, Delaugerre, C, Chaix, ML, Amiel, C, Schneider, V, Giraudeau, G, Brodard, V, Maillard, A, Plantier, JC, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, Barin, F, Chaillon, A, Marque-Juillet, S, Roque-Afonso, AM, Haïm-Boukobza, S, Flandre, P, Grudé, M, Assoumou, L, Costagliola, D, Allegre, T, Schmit, JL, and Chennebault, JM
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Infectious Diseases ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Adult ,Anti-HIV Agents ,Drug Resistance ,Viral ,Female ,France ,HIV Infections ,HIV Integrase ,HIV Protease ,HIV Reverse Transcriptase ,HIV-1 ,Heterocyclic Compounds ,3-Ring ,Humans ,Male ,Middle Aged ,Mutant Proteins ,Oxazines ,Piperazines ,Pyridones ,Quinolones ,Raltegravir Potassium ,Sequence Analysis ,DNA ,integrase ,inhibitors ,mutations ,patterns ,ANRS AC11 Resistance Study Group ,Microbiology ,Pharmacology and Pharmaceutical Sciences ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
ObjectivesThe 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 methodsData 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).ResultsAmong 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
- Published
- 2015