Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-naive individuals: Results from a European multi-cohort study

Barbara Rossetti, Massimiliano Fabbiani, Domenico Di Carlo, Francesca Incardona, Ana Abecasis, Perpetua Gomes, Anna Maria Geretti, Carole Seguin-Devaux, Federico Garcia, Rolf Kaiser, Sara Modica, Adrian Shallvari, Anders Sönnerborg, Maurizio Zazzi, A. Abecasis, M. Bobkova, M. Fabbiani, F. Garcia, A. M. Geretti, P. GomesF. Incardona, R. Kaiser, R. Paredes, B. Rossetti, M. Sayan, A. Sönnerborg, A. M. Vandamme, M. Zazzi

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2394-2399
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume76
Issue number9
DOIs
Publication statusPublished - 1 Sept 2021

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