Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting.

Greenberg, Lauren; Ryom, Lene; Wandeler, Gilles; Grabmeier-Pfistershammer, Katharina; Öllinger, Angela; Neesgaard, Bastian; Stephan, Christoph; Calmy, Alexandra; Rauch, Andri; Castagna, Antonella; Spagnuolo, Vincenzo; Johnson, Margaret; Stingone, Christof; Mussini, Cristina; De Wit, Stéphane; Necsoi, Coca; Campins, Antoni A; Pradier, Christian; Stecher, Melanie; Wasmuth, Jan-Christian; ... (2020). Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting. Journal of acquired immune deficiency syndromes JAIDS, 83(3), pp. 240-250. Wolters Kluwer Health 10.1097/QAI.0000000000002250

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BACKGROUND Despite increased 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 1/1/2012 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, 2718 (28.0%) RAL. The likelihood of starting RAL or EVG versus DTG decreased over time and was higher in Eastern and Southern Europe compared to Western Europe.At 6 months after initiation, 8.9% (95% CI 8.3%-9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, 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, 19.8% RAL).Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and prior non-AIDS defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months. CONCLUSION Uptake of DTG versus 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 due to treatment simplification.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Wandeler, Gilles and Rauch, Andri

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0894-9255

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

11 Feb 2020 09:58

Last Modified:

11 Feb 2020 09:58

Publisher DOI:

10.1097/QAI.0000000000002250

PubMed ID:

31923088

BORIS DOI:

10.7892/boris.139181

URI:

https://boris.unibe.ch/id/eprint/139181

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