engleski

The occurrence of hypersensitivity reaction and hepatotoxicity in individuals receiving integrase strand transfer inhibitors: results from the EuroSIDA study

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare but potentially serious side effects of antiretroviral use. This study aimed to establish the incidence of discontinuations due to HSR, hepatotoxicity or severe skin rash among users of dolutegravir (DTG) compared to raltegravir (RAL) or elvitegravir (EVG). Methods: HIV-positive individuals in EuroSIDA aged ≥ 18 years starting DTG-, RAL- or EVG-based combination ART (cART) between 16/01/2014 and 23/01/2019 were analysed in four groups: DTG abacavir (ABC) and RAL/EVG ABC with independent review of discontinuations to identify HSR, hepatotoxicity or severe skin rash. The incidence of discontinuation within each group was calculated. Results: In total, 4366 individuals started 5116 cART regimens including DTG, RAL or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range [IQR] 0.7 to 2.8) years per treatment episode. Median age was 51 (IQR 44 to 56) years, 3215 (73.6%) individuals were male, 2500 (57.3%) had CD4 cell counts >350 cells/μL, 166 (3.8%) were ART na€ıve and 3587 (82.2%) integrase inhibitor na€ıve at baseline. Of the treatment episodes, 3074 (60.1%) were with DTG (1738 with ABC, 1336 without) and 2042 (39.9%) were with RAL or EVG (286 with ABC, 1756 without). There were 649 discontinuations of DTG-containing regimens and 612 of RAL-/EVG-containing regimens. The discontinuation rate for any reason for DTG was 115 (95% CI 106 to 124)/1000 PYFU and 173 (95% CI 160 to 188)/1000 PYFU for RAL/EVG. The most common reasons for discontinuing an integrase inhibitor- containing regimen were toxicity and physician’s decision (Figure 1). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, 95% CI 0.04 to 1.28/1000 PYFU) and three for RAL/EVG without ABC (0.85, CI 0.18 to 2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (0.18, CI 0.00 to 0.99/1000 PYFU), and no severe skin rash discontinuation. Conclusions: During a 5-year study period in this real-world observational cohort, discontinuation rates of integrase strand transfer inhibitors (INSTI)-containing cART regimens were 50% higher among users of RAL or EVG compared to DTG. After independent review, discontinuations due to HSR or hepatotoxicity in INSTI users were very rare, indicating a low rate of severe adverse events.

Hypersensitivity ; hepatotoxicity ; inhibitors ; EuroSIDA

nije evidentirano