Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study). (27th April 2018)

• Record Type: Journal Article
• Authors: Lambert-Niclot, S; Grude, M; Chaix, M L; Charpentier, C; Reigadas, S; Le Guillou-Guillemette, H; Rodallec, A; Amiel, C; Maillard, A; Dufayard, J; Mourez, T; Mirand, A; Guinard, J; Montes, B; Vallet, S; Marcelin, A G; Descamps, D; Flandre, P; Delaugerre, C; Morand-Joubert, L
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 8(2018)
• Page Start: 2147
• Page End: 2151
• Publication Date: 2018-04-27
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky142
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) algorithm. Results: Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine ( n = 81) and abacavir/lamivudine or emtricitabine ( n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm 3 . The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L ( n = 1), I84V ( n = 2) and N88S ( n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L ( n = 2), D67N ( n = 3), K70R ( n = 1), L74I/V ( n = 3), M184V/I ( n = 16), L210W ( n = 1), T215Y/F ( n = 3) and K219Q/E ( n = 2). Conclusions: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.