Intensive Models of HCV Care for Injection Drug Users

描述(申请人提供)：在美国约500万丙型肝炎病毒感染者中，注射吸毒者(IDU)占60%。高达90%的艾滋病毒感染者也感染了丙型肝炎病毒。丙型肝炎病毒治疗导致持续病毒应答(SVR)与提高存活率有关，但到目前为止，注射吸毒者获得丙型肝炎病毒治疗的机会很少，他们在丙型肝炎病毒治疗中的成功也是有限的。虽然过去的丙型肝炎病毒治疗对1型感染的患者相对无效，但新的治疗方案已经有了实质性的改进。通过使用直接作用的抗病毒药物，在大型临床试验中进行的丙型肝炎病毒治疗可使70%以上的基因1型感染患者(包括艾滋病毒/丙型肝炎病毒混合感染患者)出现SVR或治愈，而以前的治疗方法只有45%。然而，在现实世界中，SVR比率低至14%。大多数未能实现SVR的患者会产生耐药性，但将耐药性降至最低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丙型肝炎病毒治疗，大多数注射吸毒者不仅会失败治疗并产生抗药性，而且可能会将抗药性病毒传播给其他人。因为除非我们为大多数感染丙型肝炎病毒的患者确定最佳的护理模式，否则新的丙型肝炎病毒治疗将不会实现挽救生命和节省成本的好处，所以我们提议对三种护理模式进行随机对照试验。我们之前已经开发了一个多学科的丙型肝炎病毒护理模式，将现场初级护理(包括艾滋病毒护理)、药物滥用治疗、精神护理和阿片激动剂治疗诊所内的丙型肝炎病毒相关护理整合在一起。为了最大限度地提高治疗效果，我们试行了两种与丙型肝炎病毒相关的重症监护模式：直接观察治疗(DOT)和同步团体治疗(CGT)。在我们的DOT模型中，聚乙二醇化干扰素每周给药一次，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小组内开始接受丙型肝炎病毒治疗，这提供了强大的社会支持，以减轻对副作用的恐惧，促进有效的教育，并提供每周注射。目前尚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名患有慢性丙型肝炎(基因1)的注射吸毒者(100名丙型肝炎病毒单独感染，50名艾滋病毒/丙型肝炎病毒/丙型肝炎病毒混合感染)，并随机分成三种护理模式之一：DOT、同步团体治疗或标准现场护理。我们的具体目标是：1)确定在提高依从性、SVR和降低耐药性方面，两种强化现场治疗模式(DOT或同时组治疗)中的哪一种比标准现场治疗更有效；(2)确定静脉吸毒者耐药的发生率和与耐药相关的因素；(3)对每种模式进行成本和成本-效果分析；以及(4)研究HIV合并感染对丙型肝炎病毒感染的静脉吸毒者依从性和病毒学结果的影响。

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.