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Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting

Title: Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting
Authors: Greenberg, L; Ryom, L; Wandeler, G; Grabmeier-Pfistershammer, K; Öllinger, A; Neesgaard, B; Stephan, C; Calmy, A; Rauch, A; Castagna, A; Spagnuolo, V; JOHNSON, M; Stingone, C; Mussini, C; De Wit, S; Necsoi, C; Campins, A; Pradier, C; Stecher, M; Wasmuth, J-C; Monforte, AD; Law, M; Puhr, R; Chkhartishvilli, N; Tsertsvadze, T; Garges, H; Thorpe, D; Lundgren, J; Peters, L; Bansi-Matharu, L; Mocroft, A
Source: JAIDS: Journal of Acquired Immune Deficiency Syndromes , 83 (3) pp. 240-250. (2020)
Publisher Information: Lippincott, Williams & Wilkins
Publication Year: 2020
Collection: University College London: UCL Discovery
Description: Background: Despite increased integrase strand transfer inhibitor (INSTI) use, limited large-scale, real-life data exists on INSTI uptake and discontinuation. Setting: International multicohort collaboration. Methods: RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan–Meier and Cox proportional hazards models describe time to and factors associated with discontinuation. Results: Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, and 2718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non–AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months. Conclusions: Uptake of DTG vs EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly because of treatment simplification.
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10092136/
Availability: https://discovery.ucl.ac.uk/id/eprint/10092136/3/Greenberg_Revised%20manuscript%20-%20clean%20version.pdf; https://discovery.ucl.ac.uk/id/eprint/10092136/
Rights: open
Accession Number: edsbas.3A488190
Database: BASE