大型队列研究中整合酶抑制剂（INSTIs）的使用与停用情况

Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting.

作者信息

Greenberg Lauren, Ryom Lene, Wandeler Gilles, Grabmeier-Pfistershammer Katharina, Öllinger Angela, Neesgaard Bastian, Stephan Christoph, Calmy Alexandra, Rauch Andri, Castagna Antonella, Spagnuolo Vincenzo, Johnson Margaret, Stingone Christof, Mussini Cristina, De Wit Stéphane, Necsoi Coca, Campins Antoni A, Pradier Christian, Stecher Melanie, Wasmuth Jan-Christian, Monforte Antonella d'Arminio, Law Matthew, Puhr Rainer, Chkhartishvilli Nikoloz, Tsertsvadze Tengiz, Garges Harmony, Thorpe David, Lundgren Jens D, Peters Lars, Bansi-Matharu Loveleen, Mocroft Amanda

机构信息

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom.

CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Acquir Immune Defic Syndr. 2020 Mar 1;83(3):240-250. doi: 10.1097/QAI.0000000000002250.

DOI:10.1097/QAI.0000000000002250

PMID:31923088

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.

摘要

背景

尽管整合酶链转移抑制剂（INSTI）的使用有所增加，但关于INSTI的使用和停药情况的大规模真实世界数据有限。

设置

国际多队列合作。

方法

纳入2012年1月1日后开始使用度鲁特韦（DTG）、埃替格韦（EVG）或拉替拉韦（RAL）的RESPOND参与者。使用多项逻辑回归评估使用INSTI的预测因素。Kaplan-Meier和Cox比例风险模型描述停药时间及相关因素。

结果

总体而言，共纳入9702人；5051人（52.1%）开始使用DTG，1933人（19.9%）使用EVG，2718人（28.0%）使用RAL。与DTG相比，开始使用RAL或EVG的可能性随时间降低，且在东欧和南欧高于西欧。在开始治疗6个月后，8.9%（95%置信区间：8.3%至9.5%）的人停用了INSTI（DTG为6.4%，EVG为7.4%，RAL为14.0%）。停药的主要原因是毒性（DTG为44.2%，EVG为42.5%，RAL为17.3%）。神经系统毒性在因毒性停药的DTG使用者中占比更高（DTG为31.8%，EVG为23.4%，RAL为6.6%）。总体而言，RAL的治疗简化率最高（DTG为2.7%，EVG为1.6%，RAL为19.8%）。停药风险较高的相关因素包括INSTI开始使用年份增加、女性、丙型肝炎合并感染以及既往非艾滋病定义的恶性肿瘤。东欧和南欧的个体停药可能性较小。6个月后的停药情况也有类似结果。