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Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort

d'Arminio Monforte, A; Lorenzini, P; Cozzi-Lepri, A; Mussini, C; Castagna, A; Baldelli, F; Puoti, M; ... on behalf of the Icona Foundation Study Group, .; + view all (2018) Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort. HIV Clinical Trials , 19 (2) pp. 52-60. 10.1080/15284336.2018.1440691. Green open access

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Abstract

BACKGROUND: We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-boosted darunavir (DRV/r) in the observational setting. METHODS: All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA > 200copies/mL > 6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. RESULTS: 2249 patients were included, 985 (44%) initiated ATV/r, 1023 (45%) DRV/r and 241 (11%) RAL; median follow-up of 3.6 years (IQR: 2.3-5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26% higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95%CI 1.11-1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95%CI 0.66-0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95%CI 0.24-0.87) or ATV/r (AHR 0.52, 95%CI 0.27-0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95%CI: 0.19-0.72) and ATV/r (AHR: 0.18, 95%CI: 0.09-0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95%CI 1.63-2.67) vs. DRV/r. CONCLUSIONS: In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL.

Type: Article
Title: Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/15284336.2018.1440691
Publisher version: https://doi.org/10.1080/15284336.2018.1440691
Language: English
Additional information: © 2018 Informa UK Limited, trading as Taylor & Francis Group. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cohort study, antiretroviral regimens, boosted-atazanavir, boosted-darunavir, raltegravir, therapy discontinuation
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10045414
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