Annegret Pelchen-Matthews1, Jakob Friis Larsen2, Leah Shepherd1, Josip Begovac3, Karen Pedersen4, Stéphane De Wit5, Andrzej Horban6, Elzbieta Jablonowska7, Margaret Johnson8, Irina Khromova9, Marcelo H Losso10, Lars N Nielsen11, Anna Lisa Ridolfo12, Brigitte Schmied13, Christoph Stephan14, Israel Yust15, Lloyd Curtis16, Vani Vannappagari17, Leigh Ragone17, Ashley Roen1, Dorthe Raben2, Ole Kirk2, Lars Peters2, Amanda Mocroft1,2. 1. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK. 2. CHIP Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. University Hospital of Infectious Diseases, Zagreb, Croatia. 4. Hvidovre Universitets Hospital, Hvidovre, Denmark. 5. CHU Saint-Pierre, Brussels, Belgium. 6. Wojewodzki Szpital Zakazny, Warsaw, Poland. 7. Wojewodzki Szpital Specjalistyczny, Olsztyn, Poland. 8. Royal Free & University College Medical School, London, UK. 9. Centre for HIV/AIDS and Infectious Diseases, Kaliningrad, Russia. 10. Hospital J.M. Ramos Mejia, Buenos Aires, Argentina. 11. Nordsjaellands Hospital, Hillerod, Denmark. 12. Ospedale L. Sacco, Milan, Italy. 13. SMZ, Vienna, Austria. 14. Medical Dept. 2, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. 15. Ichilov Hospital, Tel Aviv, Israel. 16. GlaxoSmithKline, London, UK. 17. ViiV Healthcare, Research Triangle, NC, USA.
Abstract
Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use.Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort. Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed. Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU). Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.
Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use.Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort. Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed. Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU). Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.
Entities:
Keywords:
Human immunodeficiency virus; antiretroviral therapy; dolutegravir; hepatotoxicity; hypersensitivity reaction; integrase strand transfer inhibitors; serious adverse events
Authors: Andrea De Vito; Annarita Botta; Marco Berruti; Valeria Castelli; Vincenzo Lai; Chiara Cassol; Alessandro Lanari; Giulia Stella; Adrian Shallvari; Antonia Bezenchek; Antonio Di Biagio Journal: J Pers Med Date: 2022-01-31