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

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.