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. 2020 Mar 1;83(3):240-250.
doi: 10.1097/QAI.0000000000002250.

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

Lauren Greenberg  1 , Lene Ryom  2 , Gilles Wandeler  3 , Katharina Grabmeier-Pfistershammer  4 , Angela Öllinger  4 , Bastian Neesgaard  2 , Christoph Stephan  5 , Alexandra Calmy  6 , Andri Rauch  3 , Antonella Castagna  7 , Vincenzo Spagnuolo  7 , Margaret Johnson  8 , Christof Stingone  8 , Cristina Mussini  9 , Stéphane De Wit  10 , Coca Necsoi  10 , Antoni A Campins  11 , Christian Pradier  12 , Melanie Stecher  13 , Jan-Christian Wasmuth  14 , Antonella d'Arminio Monforte  15 , Matthew Law  16 , Rainer Puhr  16 , Nikoloz Chkhartishvilli  17 , Tengiz Tsertsvadze  17 , Harmony Garges  18 , David Thorpe  19 , Jens D Lundgren  2 , Lars Peters  2 , Loveleen Bansi-Matharu  1 , Amanda Mocroft  1 ; RESPOND Study Group
Affiliations
Free article

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

Lauren Greenberg et al. J Acquir Immune Defic Syndr. .
Free article

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.

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