MANAGEMENT OF HEPATITIS C IN HIV-INFECTED AND UNINFECTED IDUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在美国，注射吸毒是丙型肝炎病毒的主要传播方式，大多数注射吸毒者都有丙型肝炎病毒感染。在东巴尔的摩，80%-90%的注射吸毒者感染丙型肝炎，这可能会在20年或更长时间内导致进行性肝纤维化(肝硬变)，在一些患者中，导致终末期肝病、肝细胞癌和死亡。此外，与人类免疫缺陷病毒(HIV)的混合感染存在于30%的丙型肝炎病毒感染的注射吸毒者中，并且与丙型肝炎病毒相关肝病的更快进展有关。用聚乙二醇化干扰素/利巴韦林(PEG化干扰素/利巴韦林)治疗丙型肝炎可以根除大约一半患者的丙型肝炎病毒感染。然而，使用或曾经使用注射毒品的人通常被排除在这些治疗方案之外，患有艾滋病毒感染和精神疾病等其他共病的人也是如此。这项研究旨在解决这样一个现实，即受丙型肝炎病毒感染影响最大的人受到的研究和治疗最少，随着丙型肝炎病毒治疗的成功程度的增加，这一差异变得更加引人注目。然而，由于缺乏关于艾滋病毒感染者和未感染者有资格接受丙型肝炎病毒治疗的数据，丙型肝炎病毒护理的实施受到了阻碍。为了解决这些问题，我们建议实现以下目标：1)根据绝对和相对标准确定有资格接受PEG/RBV丙型肝炎病毒治疗的艾滋病毒感染者和非感染者的比例；2)确定(由肝脏组织学和非侵入性标记物确定)艾滋病毒感染者和非感染者中有资格接受PEG/RBV治疗的丙型肝炎病毒治疗的医疗必要性；以及3)评估直接给药与标准护理递送聚乙二醇化干扰素联合利巴韦林治疗艾滋病毒感染者和非感染者丙型肝炎的安全性、耐受性、有效性和成本效益。我们预计提供的数据将对感染和不感染艾滋病毒的丙型肝炎病毒感染者的医疗保健产生重要影响，并将对制定在静脉吸毒人群中管理和提供丙型肝炎护理的政策产生重要影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Injection drug use is the predominant mode of HCV transmission in the United States and most injection drug users have HCV infection. In East Baltimore, 80-90% of IDUs are infected with hepatitis C, which can cause progressive hepatic fibrosis (cirrhosis) over 20 or more years, leading, in some patients, to end-stage liver disease, hepatocellular carcinoma and death. Furthermore, coinfection with human immunodeficiency virus (HIV) is present in 30% of HCV-infected IDUs, and is associated with the more rapid progression of HCV-related liver disease. Treatment of hepatitis C with pegylated interferon/ribavirin (PEG/RBV) eradicates HCV infection in approximately one-half of patients. However, persons who use or have used injection drugs are typically excluded from these treatment protocols, as are persons with other comorbidities such as HIV infection and psychiatric disease. This research aims to address the reality that the persons most affected by HCV infection are the least studied and the least treated, a disparity that becomes even more compelling as the success of HCV therapy increases. However, the implementation of HCV care is hindered by the paucity of data regarding which HIV-infected and uninfected IDUs are eligible and need HCV treatment. To address these issue we propose to accomplish the following aims: 1) to determine proportion of HIV-infected and uninfected IDUs who are eligible for HCV therapy with PEG/RBV according to absolute and relative criteria; 2) To determine the medical necessity of HCV treatment among HIV-infected and uninfected persons who are eligible for the PEG/RBV (determined by liver histology and non-invasive markers); and 3) To evaluate the safety, tolerability, efficacy and cost-effectiveness of directly-administered versus standard-of-care delivery of pegylated interferon alfa plus ribavirin for the treatment of hepatitis C in HIV-infected and uninfected IDUs. We anticipate providing data that will have important impact on the medical care HCV-infected IDUs with and without HIV coinfection as well as the development of policies for the management and delivery of hepatitis C care among IDUs.