Rossi Carmine, Young Jim, Martel-Laferrière Valérie, Walmsley Sharon, Cooper Curtis, Wong Alexander, Gill M John, Klein Marina B
Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, Quebec, Canada.
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
Open Forum Infect Dis. 2019 Feb 13;6(3):ofz055. doi: 10.1093/ofid/ofz055. eCollection 2019 Mar.
There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV-a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients.
We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure.
Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure-particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38-6.0; posterior OR, 1.0; 95% CrI, 0.40-2.5).
DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure.
关于直接抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）合并感染患者的真实世界有效性的数据有限，这一人群面临着包括持续药物使用、肝硬化和其他合并症等复杂挑战。我们评估了患者特征以及根据指南选择HCV治疗方案的适宜性如何影响合并感染患者的治疗结果。
我们纳入了2013年11月至2017年7月在加拿大合并感染队列中开始接受DAA治疗的所有患者。持续病毒学应答（SVR）定义为治疗后10至18周测得的HCV RNA检测不到。我们将治疗失败定义为病毒学失败、复发或未实现SVR而死亡。采用贝叶斯逻辑回归来估计与治疗失败的患者人口统计学、临床和治疗相关风险因素相关的后验比值比（OR）。
295例患者开始使用DAA；31%有治疗经验，29%为肝硬化患者，80%为HCV基因1型。总体而言，92%实现了SVR（286例中的263例，9例情况不明），女性的SVR率最高（97%），肝硬化患者（88%）和高频注射吸毒者（89%）的SVR率最低。许多患者（38%）被开具了超出当前临床指南的治疗方案。这并没有明显增加治疗失败的风险——尤其是在基因1型患者中（先前比值比[OR]，1.5；95%可信区间[CrI]，0.38 - 6.0；后验OR，1.0；95% CrI，0.40 - 2.5）。
尽管使用了未按标签说明、疗效较差的治疗方案，但在一个多样化的真实世界合并感染队列中，DAA的效果比预期更有效。高频注射吸毒和肝硬化与失败风险增加相关。
