Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.
CHIP Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
HIV Res Clin Pract. 2021 Dec;22(6):160-168. Epub 2021 Nov 15.
Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use. 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. 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. 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). 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.
超敏反应 (HSR) 和肝毒性是抗逆转录病毒治疗的罕见但潜在严重的副作用。为了研究在 EuroSIDA 队列中，与拉替拉韦（RAL）或艾维雷格（EVG）相比，多替拉韦（DTG）使用者因 HSR、肝毒性或其他原因停药的情况。我们比较了年龄≥18 岁且开始联合抗逆转录病毒治疗（ART，≥3 种药物）的个体，他们使用 DTG 与 RAL 或 EVG 联合治疗，有无阿巴卡韦（ABC），时间为 2014 年 1 月 16 日至 2019 年 1 月 23 日。严重不良事件（SAE）导致的停药情况由独立审查。共有 4366 人开始了 5116 种包含 DTG、RAL 或 EVG 的 ART 方案，共随访 9180 人年（PYFU），每个治疗期的中位随访时间为 1.6 年（四分位距 0.7-2.8）。其中，3074 人（60.1%）使用了 DTG（1738 人含 ABC，1336 人不含 ABC），2042 人（39.9%）使用了 RAL 或 EVG（286 人含 ABC，1756 人不含 ABC）。1261 例 INSTI 方案停药，其中含 DTG 的方案 649 例（停药率为 115，95%CI 106-124/1000PYFU），含 RAL 或 EVG 的方案 612 例（停药率为 173，CI 160-188/1000PYFU）。经过独立审查，有 5 例 HSR 停药，其中 2 例与 DTG 相关（1 例含 ABC，1 例不含 ABC，停药率为 0.35，95%CI 0.04-1.28/1000PYFU），3 例与 RAL 或 EVG 相关，不含 ABC（0.85，95%CI 0.18-2.48/1000PYFU）。1 例含 ABC 的 DTG 出现肝毒性停药（停药率为 0.18，95%CI 0.00-0.99/1000PYFU）。在 EuroSIDA 队列的 5 年观察期间，HSR 或肝毒性导致的停药情况非常罕见，表明严重不良事件发生率较低。
