TY - JOUR
T1 - Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors
T2 - results from the EuroSIDA study
AU - for the EuroSIDA Study Group
AU - Pelchen-Matthews, Annegret
AU - Larsen, Jakob Friis
AU - Shepherd, Leah
AU - Begovac, Josip
AU - Pedersen, Karen
AU - De Wit, Stéphane
AU - Horban, Andrzej
AU - Jablonowska, Elzbieta
AU - Johnson, Margaret
AU - Khromova, Irina
AU - Losso, Marcelo H.
AU - Nielsen, Lars N.
AU - Ridolfo, Anna Lisa
AU - Schmied, Brigitte
AU - Stephan, Christoph
AU - Yust, Israel
AU - Curtis, Lloyd
AU - Vannappagari, Vani
AU - Ragone, Leigh
AU - Roen, Ashley
AU - Raben, Dorthe
AU - Kirk, Ole
AU - Peters, Lars
AU - Mocroft, Amanda
N1 - Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Human immunodeficiency virus
KW - antiretroviral therapy
KW - dolutegravir
KW - hepatotoxicity
KW - hypersensitivity reaction
KW - integrase strand transfer inhibitors
KW - serious adverse events
UR - http://www.scopus.com/inward/record.url?scp=85119623490&partnerID=8YFLogxK
U2 - 10.1080/25787489.2021.2003132
DO - 10.1080/25787489.2021.2003132
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AN - SCOPUS:85119623490
SN - 2578-7489
VL - 22
SP - 160
EP - 168
JO - HIV Research and Clinical Practice
JF - HIV Research and Clinical Practice
IS - 6
ER -