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Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting

D'Arminio Monforte, A; Cozzi-Lepri, A; Di Biagio, A; Marchetti, G; Lo Caputo, S; Rusconi, S; Gianotti, N; ... ICONA Foundation Study Group, .; + view all (2019) Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting. Journal of Antimicrobial Chemotherapy , 74 (5) pp. 1363-1367. 10.1093/jac/dky566. Green open access

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Abstract

OBJECTIVES: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. METHODS: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs  ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan–Meier and Cox regression. RESULTS: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2–3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2–2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00–3.76, P = 0.05). CONCLUSIONS: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.

Type: Article
Title: Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dky566
Publisher version: https://doi.org/10.1093/jac/dky566
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: HIV, cd4 count determination procedure, HIV seropositivity, integrase inhibitors, plasma, treatment failure, virology, toxic effect, risk reduction, cox proportional hazards models, elvitegravir, raltegravir, surrogate endpoints, cobicistat, dolutegravir, time-to-treatment
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/10067602
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