Rossetti, BarbaraFabbiani, MassimilianoDi Carlo, DomenicoIncardona, F.Abecasis, A.Gomes, PerpetuaGeretti, A. M.Seguin-Devaux, C.Garcia, FedericoKaiser, RolfModica, SaraShallvari, AdrianSönnerborg, A.Zazzi, M.Bobkova, M.Seguin-Devaux, C.Paredes, R.Sayan, M.Vandamme, A. M.2021-09-242021-09-242021-09-010305-7453PURE: 33793803PURE UUID: 3024eecf-813b-42f6-9c2f-1fb43428c297Scopus: 85114380094PubMed: 34212176http://hdl.handle.net/10362/125098Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.Background: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. Conclusions: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.6338044engPharmacologyMicrobiology (medical)Infectious DiseasesPharmacology (medical)SDG 3 - Good Health and Well-beingSDG 9 - Industry, Innovation, and InfrastructureSDG 12 - Responsible Consumption and Productionjournal article10.1093/jac/dkab200https://www.scopus.com/pages/publications/85114380094