Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study)

• Published in: Journal of antimicrobial chemotherapy Vol. 73; no. 8; pp. 2147 - 2151
• Main 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
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 01.08.2018
• Subjects: Human health and pathology; Infectious diseases; Life Sciences; Microbiology and Parasitology; Virology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dky142

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. 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. 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/mm3. 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). 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.