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

Greenberg, L; Ryom, L; Wandeler, G; Grabmeier-Pfistershammer, K; Öllinger, A; Neesgaard, B; Stephan, C; ... Mocroft, A; + view all (2020) Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting. JAIDS: Journal of Acquired Immune Deficiency Syndromes , 83 (3) pp. 240-250. 10.1097/QAI.0000000000002250.

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Abstract

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.

Type: Article
Title: Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting
DOI: 10.1097/QAI.0000000000002250
Publisher version: https://doi.org/10.1097/QAI.0000000000002250
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.
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
URI: https://discovery.ucl.ac.uk/id/eprint/10092136
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