Lauren Greenberg1, Lene Ryom2, Gilles Wandeler3, Katharina Grabmeier-Pfistershammer4, Angela Öllinger4, Bastian Neesgaard2, Christoph Stephan5, Alexandra Calmy6, Andri Rauch3, Antonella Castagna7, Vincenzo Spagnuolo7, Margaret Johnson8, Christof Stingone8, Cristina Mussini9, Stéphane De Wit10, Coca Necsoi10, Antoni A Campins11, Christian Pradier12, Melanie Stecher13, Jan-Christian Wasmuth14, Antonella d'Arminio Monforte15, Matthew Law16, Rainer Puhr16, Nikoloz Chkhartishvilli17, Tengiz Tsertsvadze17, Harmony Garges18, David Thorpe19, Jens D Lundgren2, Lars Peters2, Loveleen Bansi-Matharu1, Amanda Mocroft1. 1. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom. 2. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 4. Wiener Medizinische Universität, Vienna, Austria. 5. Frankfurt HIV Cohort Study, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany. 6. Swiss HIV Cohort Study (SHCS), University of Zurich, Zurich, Switzerland. 7. San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy. 8. The Royal Free HIV Cohort Study, Royal Free Hospital, University College London, London, United Kingdom. 9. Modena HIV Cohort, Università degli Studi di Modena, Modena, Italy. 10. CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium. 11. PISCIS Cohort Study, HIV Unit, Department of Internal Medicine, Hospital Son Espases de Mallorca, Spain. 12. Nice HIV Cohort, Université Côte d'Azur et Centre Hospitalier Universitaire, Nice, France. 13. University Hospital Cologne, Cologne, Germany. 14. University Hospital Bonn, Bonn, Germany. 15. Italian Cohort Naïve Antiretrovirals (ICONA), ASST Santi Paolo e Carlo, Milano, Italy. 16. The Australian HIV Observational Database (AHOD), UNSW, Sydney, Australia. 17. Georgian National AIDS Health Information System (AIDS HIS), Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia. 18. ViiV Healthcare, RTP, NC; and. 19. Gilead science, Foster City, CA.
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.
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.
Authors: Lauren Greenberg; Lene Ryom; Bastian Neesgaard; Gilles Wandeler; Therese Staub; Martin Gisinger; Michael Skoll; Huldrych F Günthard; Alexandra Scherrer; Cristina Mussini; Colette Smith; Margaret Johnson; Stéphane De Wit; Coca Necsoi; Christian Pradier; Ferdinand Wit; Clara Lehmann; Antonella d'Arminio Monforte; Jose M Miró; Antonella Castagna; Vincenzo Spagnuolo; Anders Sönnerborg; Matthew Law; Jolie Hutchinson; Nikoloz Chkhartishvili; Natalia Bolokadze; Jan-Christian Wasmuth; Christoph Stephan; Vani Vannappagari; Felipe Rogatto; Josep M Llibre; Claudine Duvivier; Jennifer Hoy; Mark Bloch; Heiner C Bucher; Alexandra Calmy; Alain Volny Anne; Annegret Pelchen-Matthews; Jens D Lundgren; Lars Peters; Loveleen Bansi-Matharu; Amanda Mocroft Journal: Clin Infect Dis Date: 2021-10-05 Impact factor: 20.999
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Authors: Dathan M Byonanebye; Mark N Polizzotto; Bastian Neesgaard; Mario Sarcletti; Raimonda Matulionyte; Dominique L Braun; Antonella Castagna; Stéphane de Wit; Ferdinand Wit; Eric Fontas; Jörg Janne Vehreschild; Jan Vesterbacka; Lauren Greenberg; Camilla Hatleberg; Harmony Garges; Joel Gallant; Alain Volny Anne; Angela Öllinger; Iwona Mozer-Lisewska; Bernard Surial; Vincenzo Spagnuolo; Coca Necsoi; Marc van der Valk; Amanda Mocroft; Matthew Law; Lene Ryom; Kathy Petoumenos Journal: HIV Med Date: 2022-03-01 Impact factor: 3.094