多中心随机对照试验（INTRO-HCV）：对注射吸毒者丙型肝炎病毒感染的综合治疗。
Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV).
机构信息
Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Norway.
出版信息
PLoS Med. 2021 Jun 1;18(6):e1003653. doi: 10.1371/journal.pmed.1003653. eCollection 2021 Jun.
BACKGROUND
The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID.
METHODS AND FINDINGS
INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment.
CONCLUSIONS
Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV.
TRIAL REGISTRATION
ClinicalTrials.gov.no NCT03155906.
背景
在三级医疗机构中，丙型肝炎病毒（HCV）感染的标准检测和治疗途径对注射吸毒者（PWID）来说难以企及。本研究旨在评估综合治疗方案对 PWID 慢性 HCV 感染的疗效。
方法和发现
INTRO-HCV 是一项多中心、随机对照临床试验。2017 年至 2019 年期间，在挪威的阿片类药物替代治疗（OAT）和社区护理诊所招募参与者，并按 1:1 比例随机分配至 2 种治疗组。在阿片类药物替代治疗诊所或社区护理中心（CCCs），由多学科团队为物质使用障碍者提供综合治疗。这包括现场 HCV 检测、肝纤维化评估、咨询、治疗和治疗后随访。标准治疗在医院门诊进行。两组均给予口服直接作用抗病毒（DAA）药物。该研究未完全设盲。主要结局是治疗开始时间和持续病毒学应答（SVR），定义为治疗完成后 12 周时 HCV RNA 不可检测，采用意向治疗进行分析，并以风险比（HR）和比值比（OR）及其 95%置信区间表示。在纳入的 298 名参与者中，150 名被随机分配至标准治疗组，其中 116/150（77%）开始治疗，108/150（72%）在转诊后 1 年内开始治疗。在被随机分配至综合护理组的 148 名参与者中，145/148（98%）开始治疗，141/148（95%）在转诊后 1 年内开始治疗。与标准治疗相比，综合治疗组的治疗开始时间 HR 为 2.2（1.7 至 2.9）。综合治疗组的 SVR 确证率为 123（已开始治疗者的 85%/所有开始治疗者的 83%），标准治疗组为 96（已开始治疗者的 83%/所有开始治疗者的 64%）（治疗者中的 OR：1.5 [0.8 至 2.9]，所有参与者中的 OR：2.8 [1.6 至 4.8]）。未发现与治疗相关的严重不良事件。
结论
与标准治疗相比，PWID 的 HCV 综合治疗在治疗开始时间方面更具优势，随后更多人实现 SVR。在开始治疗的人群中，SVR 率相当。扩大综合治疗模式可能是消除 HCV 的重要工具。
试验注册
ClinicalTrials.gov.no NCT03155906。
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