HCV Disease Management in HIV- HCV Coinfected IDUs

描述（由申请方提供）：R 01 DA 16065主要针对HIV感染的注射吸毒者（IDUs）中的丙型肝炎病毒（HCV）感染。在感染艾滋病毒的注射吸毒者中，HCV疾病是发病和死亡的主要原因。尽管医学上的紧迫性，关于HCV疾病及其管理的基本问题还没有得到最终的回答。严重肝病的真实患病率尚不清楚，因为估计数来自于转诊接受HCV治疗后接受肝活检的HIV感染者。此外，由于肝活检的适用性有限，关于HCV疾病分期与临床重要结局（如终末期肝病（ESLD））之间关系的数据很少。虽然CD 4细胞和HIV RNA定量是用于对HIV疾病风险进行分层并确定治疗需求的强有力的非侵入性措施，但尚未为HCV疾病建立此类非侵入性预后标志物。最后，HIV感染者注射吸毒者中HCV疾病的管理具有挑战性;我们的研究表明，HIV感染者的HCV净治疗有效性较低。直到最近，在合并感染的注射吸毒者中HCV疾病研究的一个主要限制是疾病阶段的测量。瞬时弹性成像是一种新的，非侵入性的方法，基于肝纤维化增加时肝脏弹性降低的观察。可以在临床上获得快速的肝硬度测量以确定HCV疾病阶段。我们的研究表明，通过评估肝硬度可以准确、安全地测量合并感染的静脉吸毒者的HCV疾病。在我们的第一个目标中，我们将应用这种新的方法来确定HCV疾病的人口患病率在合并感染的注射吸毒者独立的转诊HCV治疗，提供真正的HCV疾病负担的第一个有效的估计。在我们的第二个目标中，我们将询问HCV疾病结局的显著差异（例如，ESLD）可以通过弹性成像评估的肝脏硬度来解释;我们将检验肝脏硬度增加与ESLD事件风险增加相关的假设。我们的第三个目标将测试的假设，一个高度创新的行为强化（或有凭证激励）将提高目前和未来的HCV治疗合并感染的注射吸毒者的有效性。HCV疾病仍然是艾滋病毒感染者面临的一个重大挑战。这些基本问题的答案是需要推进这一领域，并将提供急需的数据，以影响政策和准则的制定，HCV疾病的管理，在艾滋病毒感染的注射吸毒者死亡的主要原因。 公共卫生相关性：该应用程序的重点是HIV感染的注射吸毒者（IDUs）中的丙型肝炎病毒（HCV）感染。在感染艾滋病毒的注射吸毒者中，HCV疾病是发病和死亡的主要原因。本研究采用两种高度创新的干预措施，瞬时弹性成像和应急行为强化，以评估和管理的人与艾滋病毒/丙型肝炎病毒合并感染。

DESCRIPTION (provided by applicant): R01DA16065 is focused on hepatitis C virus (HCV) infection in HIV-infected injection drug users (IDUs). Among HIV-infected IDUs, HCV disease is a leading cause of morbidity and mortality. Despite the medical urgency, fundamental questions about HCV disease and its management have not been conclusively answered. The true prevalence of significant liver disease is unknown, since estimates have been derived from HIV-infected persons who underwent liver biopsy following referral for HCV treatment. Further, due to limited applicability of liver biopsy, few data exist regarding the relationship of HCV disease stage and clinically important outcomes such as end-stage liver disease (ESLD). While CD4 cell and HIV RNA quantification are powerful non-invasive measures used to stratify HIV disease risk and define the need for treatment, such non-invasive, prognostic markers have not been established for HCV disease. Finally, the management of HCV disease in HIV-infected IDUs is challenging; our research has shown that net HCV treatment effectiveness is low in HIV-infected persons. Until recently, a major limitation to HCV disease research in coinfected IDUs has been the measurement of disease stage. Transient elastography is a novel, non-invasive method based on the observation that liver elasticity decreases as liver fibrosis increases. Rapid liver stiffness measurements can be obtained in the clinic to determine HCV disease stage. Our research has shown that HCV disease in coinfected IDUs can be accurately and safely measured by assessment of liver stiffness. In our first aim, we will apply this novel method to determine the population prevalence of HCV disease in coinfected IDUs independent of referral for HCV treatment, providing one of the first valid estimates of the true HCV disease burden. In our second aim, we will ask whether the marked differences in HCV disease outcomes (e.g., ESLD) can be explained by liver stiffness as assessed by elastography; we'll test the hypothesis that increased liver stiffness is associated with greater risk of incident ESLD. Our third aim will test the hypothesis that a highly innovative behavioral reinforcement (contingent voucher incentives) will improve the effectiveness of current and future HCV treatments in coinfected IDUs. HCV disease remains a significant unmet challenge in HIV-infected persons. Answers to these fundamental questions are needed to advance this field and will provide much needed data to influence the development of policies and guidelines for the management of HCV disease, a leading cause of death in HIV-infected IDUs. PUBLIC HEALTH RELEVANCE: The application is focused on hepatitis C virus (HCV) infection in HIV-infected injection drug users (IDUs). Among HIV-infected IDUs, HCV disease is a leading cause of morbidity and mortality. This research applies two highly innovative interventions, transient elastography and contingent behavioral reinforcement, to the evaluation and management of persons with HIV/HCV coinfection.