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%。高达90%的感染艾滋病毒的注射吸毒者也感染了HCV。导致持续病毒应答（SVR）的HCV治疗与生存率增加相关，但迄今为止，注射吸毒者获得HCV治疗的机会很少，他们在HCV治疗方面的成功有限。虽然过去的HCV治疗在基因型1感染的患者中相对无效，但新的治疗方案得到了实质性的改善。使用直接作用的抗病毒药物，在大型临床试验中提供的HCV治疗导致超过70%的基因型1感染患者（包括HIV/HCV合并感染患者）的SVR或治愈，而先前治疗的比例为45%。然而，在现实世界中，SVR率低至14%。大多数未能实现SVR的患者将产生耐药性，但最大限度地减少耐药性的最佳依从性水平尚不清楚。如果继续在目前的护理模式下提供HCV治疗，大多数注射吸毒者不仅治疗失败并产生耐药性，而且可能将耐药病毒传播给他人。由于新的HCV治疗的生命和成本节约的好处将无法实现，除非我们确定最佳模式的照顾大多数HCV感染的患者，我们提出了一个随机对照试验的三种模式的照顾。我们以前已经开发了一个多学科的HCV护理模式，它整合了现场初级保健（包括艾滋病毒护理），药物滥用治疗，精神病护理和阿片类药物激动剂治疗诊所内的HCV相关护理。为了最大限度地提高治疗效果，我们试行了两种HCV相关强化护理模式：直接观察治疗（DOT）和同期团体治疗（CGT）。在我们的DOT模型中，聚乙二醇干扰素每周给药一次，每天一次口服药物在美沙酮窗口给药。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，并提供每周注射。目前还不清楚这两种模式是否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名患有慢性HCV（基因型1）的注射吸毒者（100名HCV单感染者和50名HIV/HCV合并感染者），并随机分配至三种护理模式之一：DOT;同期组治疗;或标准现场护理。我们的具体目标是：1）确定两种强化现场HCV治疗模式中的任一种（2）确定静脉吸毒者耐药的发生率和相关因素;（3）对每种治疗模式进行成本和成本效果分析;（4）对每种治疗模式进行评价。（4）探讨HIV合并感染对HCV感染的静脉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.