Resistance to integrase inhibitors: a national study in HIV -1-infected treatment-naive and -experienced patients

Anne-Geneviève Marcelin (1, 2) , Maxime Grude (1, 2) , Charlotte Charpentier (3, 4) , Pantxika Bellecave (5, 6) , Laura Le Guen (7) , Coralie Pallier (8) , Stéphanie Raymond (9, 10) , Audrey Mirand (11) , Laurence Bocket (12) , Djeneba Bocar Fofana (1, 13) , Constance Delaugerre (14) , Thuy Nguyen (1, 2) , Brigitte Montes (15) , Helène Jeulin (16) , Thomas Mourez (17) , Samira Fafi-Kremer (18) , Corinne Amiel (19) , Catherine Roussel (20) , Julia Dina (21) , Mary-Anne Trabaud (22) , Hélène Le Guillou-Guillemette (23) , Sophie Vallet (24) , Anne Signori-Schmuck (25) , Anne Maillard (26) , Virginie Ferré (27) , Diane Descamps (4, 3) , Vincent Calvez (1, 2) , Philippe Flandre (1, 2)

1 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 Service de Virologie [CHU Pitié-Salpêtrière]
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
5 MFP - Microbiologie Fondamentale et Pathogénicité
6 Service de virologie et unité de surveillance biologique [Bordeaux]
7 CHU Nantes - Centre hospitalier universitaire de Nantes
8 Hôpital Paul Brousse
9 CPTP - Centre de Physiopathologie Toulouse Purpan
10 Laboratoire Virologie [CHU Toulouse]
11 CHU Clermont-Ferrand
12 CHU Lille
13 Laboratoire de Virologie [CHU Saint-Antoine]
14 Laboratoire de Virologie [CHU Saint-Louis]
15 CHRU Montpellier - Hôpital Saint Eloi
16 Service de Virologie [CHRU Nancy]
17 CHU Rouen
18 CHU Strasbourg
19 CHU Tenon [AP-HP]
20 CHU Amiens-Picardie
21 Service de Virologie [CHU Caen]
22 Hôpital de la Croix-Rousse [CHU - HCL]
23 CHU Angers - Centre Hospitalier Universitaire d'Angers
24 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest
25 CHU - Centre Hospitalier Universitaire [Grenoble]
26 CHU Pontchaillou [Rennes]
27 CIC Nantes - Centre d’Investigation Clinique de Nantes

Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice. Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated. Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure. Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology; Life Sciences [q-bio]; Microbiology and Parasitology

Anne-Geneviève Marcelin, Maxime Grude, Charlotte Charpentier, Pantxika Bellecave, Laura Le Guen, et al.. Resistance to integrase inhibitors: a national study in HIV -1-infected treatment-naive and -experienced patients. Journal of Antimicrobial Chemotherapy, 2019, 74 (5), pp.1368-1375. ⟨10.1093/jac/dkz021⟩. ⟨hal-02154049⟩