Morris Meghan D, McDonell Claire, Luetkemeyer Annie F, Thawley Robert, McKinney Jeff, Price Jennifer C
Department of Epidemiology and Biostatistics, University of California, San Francisco.
Department of Medicine, University of California, San Francisco.
JAMA Netw Open. 2023 Oct 2;6(10):e2338792. doi: 10.1001/jamanetworkopen.2023.38792.
IMPORTANCE: Disparities persist in testing and treatment for hepatitis C virus (HCV), leaving socially marginalized populations less likely to benefit from curative treatment. Linkage services are often insufficient to overcome barriers to navigating the medical system and contextual factors. OBJECTIVE: To determine the feasibility, acceptability, and safety of HCV treatment at the point of HCV infection diagnosis disclosure in a nonclinical community setting. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm nonrandomized controlled trial conducted between July 1, 2020, and October 31, 2021, street-outreach recruitment targeted people experiencing homelessness and injecting drugs in an urban US community who were eligible for simplified HCV treatment. INTERVENTIONS: Study procedures were designed to reflect the community environment and services needed to provide HCV testing, disclosure, and treatment in a nonclinical site. The test-and-treat No One Waits (NOW) model of care provided a 2-week starter pack of 400 mg of sofosbuvir and 100 mg of velpatasvir at time of HCV RNA results disclosure. Participants were transitioned to insurance-provided sofosbuvir-velpatasvir when feasible to complete a 12-week treatment course. MAIN OUTCOMES AND MEASURES: The primary end point was sustained virologic response at posttreatment week 12 or later (SVR12). Acceptability end points were treatment initiation and completion. Safety end points were treatment discontinuation because of a late exclusion criterion and adverse events. RESULTS: Of the 492 people (median [IQR] age, 48 [37-58] years; 62 [71%] male) who underwent anti-HCV testing, 246 (50%) tested anti-HCV positive, and 111 (23%) tested HCV RNA positive and were eligible for simplified HCV treatment. Eighty-nine of the 111 eligible participants (80%) returned for confirmatory RNA results, and 87 (98%) accepted and initiated HCV treatment. Seventy (80%) were currently injecting drugs, 83 (97%) had an income below the poverty line, and 53 (61%) were currently unsheltered. Most had HCV genotype 1a (45 [52%]) or 3 (20 [23%]). Sixty-nine (79%) completed 12 weeks of sofosbuvir-velpatasvir treatment, 2 stopped treatment because of low adherence, and 16 were lost to follow-up. Of the 66 participants who completed treatment and had a successful blood draw, 61 (92%) had undetectable HCV RNA at treatment completion. Of the 87 treated patients, 58 achieved SVR12, leading to a treatment response of 67% (95% CI, 56%-76%) among the intention-to-treat group and 84% (95% CI, 73%-92%) among the per-protocol group. There were no adverse events, late exclusions, or deaths. CONCLUSIONS AND RELEVANCE: In this nonrandomized controlled trial of HCV treatment at the point of diagnosis, the NOW model of care reduced steps between HCV testing and treatment initiation and resulted in high levels of treatment initiation, completion, and cure. The NOW model of care can expand the current HCV test-and-treat toolkit by reaching a broader population of marginalized communities and expediting curative therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03987503.
重要性:丙型肝炎病毒(HCV)检测和治疗方面的差距依然存在,使得社会边缘化人群从治愈性治疗中获益的可能性较低。衔接服务往往不足以克服医疗系统导航障碍和背景因素。 目的:确定在非临床社区环境中,在HCV感染诊断披露时进行HCV治疗的可行性、可接受性和安全性。 设计、设置和参与者:在2020年7月1日至2021年10月31日进行的这项单臂非随机对照试验中,街头外展招募针对美国城市社区中符合简化HCV治疗条件的无家可归者和注射吸毒者。 干预措施:研究程序旨在反映在非临床场所提供HCV检测、披露和治疗所需的社区环境和服务。“无人等待”(NOW)检测与治疗护理模式在HCV RNA结果披露时提供为期2周的400毫克索磷布韦和100毫克维帕他韦起始药包。可行时,参与者转为由保险提供的索磷布韦-维帕他韦,以完成12周的治疗疗程。 主要结局和测量指标:主要终点是治疗后第12周或更晚的持续病毒学应答(SVR12)。可接受性终点是治疗开始和完成。安全性终点是因后期排除标准和不良事件而停药。 结果:在492名接受抗HCV检测的人(年龄中位数[四分位间距]为48[37 - 58]岁;62[71%]为男性)中,246人(50%)抗HCV检测呈阳性,111人(23%)HCV RNA检测呈阳性且符合简化HCV治疗条件。111名符合条件的参与者中有89人(80%)返回获取确认的RNA结果,87人(98%)接受并开始HCV治疗。70人(80%)目前正在注射吸毒,83人(97%)收入低于贫困线,53人(61%)目前无住所。大多数人感染的是HCV 1a基因型(45[52%])或3基因型(20[23%])。69人(79%)完成了12周的索磷布韦-维帕他韦治疗,2人因依从性差停药,16人失访。在66名完成治疗且采血成功的参与者中,61人(92%)在治疗结束时HCV RNA检测不到。在87名接受治疗的患者中,58人实现了SVR12,意向性治疗组的治疗应答率为67%(95%CI,56% - 76%),符合方案组为84%(95%CI,73% - 92%)。没有不良事件、后期排除或死亡情况。 结论与意义:在这项诊断时HCV治疗的非随机对照试验中,NOW护理模式减少了HCV检测与治疗开始之间的步骤,并导致了高水平的治疗开始、完成和治愈。NOW护理模式可通过覆盖更广泛的边缘化社区人群并加快治愈性治疗,来扩展当前的HCV检测与治疗方法。 试验注册:ClinicalTrials.gov标识符:NCT03987503。
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