Intensive Models of HCV Care for Injection Drug Users

描述（由申请人提供）：注射吸毒者（IDUs）占美国约500万丙型肝炎病毒（HCV）感染者的60%。在感染艾滋病毒的注射吸毒者中，高达90%也感染了丙型肝炎病毒。HCV治疗导致的持续病毒反应（SVR）与生存率增加有关，但迄今为止，注射吸毒者获得HCV治疗的机会很少，他们在HCV治疗中的成功受到限制。尽管过去的丙型肝炎病毒治疗在基因型1感染患者中相对无效，但新的治疗方案有了很大的改善。使用直接作用的抗病毒药物，在大型临床试验中提供的HCV治疗在超过70%的基因型1感染患者（包括HIV/HCV合并感染患者）中导致SVR或治愈，而以前的治疗为45%。然而，在现实环境中，SVR率低至14%。大多数未达到SVR的患者会产生耐药性，但减少耐药性的最佳依从性水平尚不清楚。如果丙型肝炎病毒治疗继续在目前的护理模式下进行，大多数注射毒品者不仅无法治疗并产生耐药性，而且可能将耐药病毒传播给他人。因为除非我们确定大多数HCV感染患者的最佳护理模式，否则新的HCV治疗方法的生命和成本节约效益将无法实现，因此我们建议进行三种护理模式的随机对照试验。我们之前已经开发了HCV治疗的多学科模型，将现场初级护理（包括HIV治疗）、药物滥用治疗、精神病学治疗和阿片类激动剂治疗诊所的HCV相关护理整合在一起。为了最大限度地提高治疗效果，我们试点了两种强化hcv相关护理模式：直接观察治疗（DOT）和并发群体治疗（CGT）。在我们的DOT模型中，聚乙二醇化干扰素每周给药一次，在美沙酮窗口期每天口服一次药物。在我们的CGT模型中，患者在每周一次的治疗组中开始HCV治疗，该治疗组提供强大的社会支持，以减轻对副作用的恐惧，促进有效的教育，并提供每周一次的注射。目前尚不清楚哪种模式比标准的现场护理更好或更具成本效益。在拟议的研究中，将从美沙酮诊所招募150名慢性HCV（基因型1）的idu（100名HCV单感染和50名HIV/HCV共感染），并随机分配到三种护理模式之一：DOT；同期组内治疗；或者标准的现场护理。我们的具体目的是：1)确定两种强化现场HCV治疗模式（DOT或同时组治疗）是否比标准现场治疗更有效，以提高依从性和SVR，并降低耐药；(2)确定注射吸毒者耐药发生率及相关因素；(3)对每个模型进行成本和成本效益分析；(4)研究HIV合并感染对丙型肝炎病毒注射吸毒者依从性和病毒学结局的影响。

DESCRIPTION (provided by applicant):Injection drug users (IDUs) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Up to 90% of HIV-infected IDUs are also infected with HCV. HCV treatment leading to sustained viral response (SVR) is associated with increased survival, but to date IDUs have had poor access to HCV care and their success in HCV treatment has been limited. Although past HCV therapies have been relatively ineffective in genotype-1 infected patients, newer regimens are substantially improved. With direct-acting antiviral agents, HCV treatment delivered within large clinical trials leads to SVR or cure in over 70% of genotype-1 infected patients (including HIV/HCV-coinfected patients), compared to 45% with previous therapies. However, SVR rates are as low as 14% in real-world settings. The majority of patients who fail to achieve SVR will develop drug resistance, but the optimal adherence level to minimize resistance is unknown. If HCV treatment continues to be delivered within current models of care, most IDUs will not only fail treatment and develop resistance, but may transmit resistant viruses to others. Because the life- and costsaving benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients, we are proposing a randomized controlled trial of three models of care. We have previously developed a multidisciplinary model of HCV care which integrates on-site primary care (including HIV care), substance abuse treatment, psychiatric care, and HCV-related care within opiate agonist treatment clinics. To maximize treatment outcomes, we piloted two models of intensive HCV-related care: directly observed therapy (DOT), and concurrent group therapy (CGT). In our DOT model, pegylated interferon is administered once weekly, and one daily dose of oral medication is administered at the methadone window. In our CGT model, patients initiate HCV treatment within a once weekly treatment group which provides powerful social support to mitigate fears of side effects, promote efficient education, and deliver weekly injections. It is unknown whether either model is better or more cost-effective than standard on-site care. In the proposed study, 150 IDUs (100 HCV-monoinfected and 50 HIV/HCV coinfected) with chronic HCV (genotype 1) will be recruited from methadone clinics and randomized to one of three models of care: DOT; concurrent group treatment; or standard on-site care. Our specific aims are: 1) To determine whether either of two intensive on-site HCV treatment models (DOT or concurrent group treatment) is more efficacious than standard on-site treatment for enhancing adherence and SVR, and decreasing drug resistance; (2) To determine the incidence and factors associated with the development of drug resistance in IDUs; (3) To perform cost and cost-effectiveness analyses of each model; and (4) To examine the impact of HIV coinfection on adherence and virologic outcomes among HCV-infected IDUs.