Optimizing Care for HIV/HCV-Coinfected Patients in the New HCV Treatment Era

项目总结/摘要 这个K 01奖将提供培训和指导的研究经验，我需要成为一个 一个独立的研究人员，重点是改善患者的健康结果或有风险的慢性 病毒感染慢性丙型肝炎病毒（HCV）感染影响美国超过300万人，8万 每年HCV相关死亡人数HCV对健康的影响在人类免疫缺陷病毒中更为严重 (HIV)HCV相关肝病是非艾滋病相关死亡的主要原因。 HIV/HCV合并感染也与肝外结局风险增加有关，包括 心血管和肾脏疾病。随着无干扰素治疗方案的出现，大多数HCV患者可以 无论艾滋病毒感染状况如何，都可以治愈。然而，关键的问题仍然是：1）时间的影响， HCV治疗对肝和肝外结局的影响，2）肝和肝外持续风险 HCV治愈后的结果，以及3）HCV治疗在肝病早期阶段是否有临床益处 值得在这些患者中使用昂贵的新方案。HIV/HCV合并感染的高危人群 患者是研究这些问题的理想选择，原因有二。首先，由于HIV/HCV合并感染患者 是HCV治疗的优先群体，他们将在一系列肝病阶段接受治疗， 提供了一个独特的机会来调查HCV治疗决策的临床和经济影响。 其次，HCV治愈后HCV相关结局的持续风险可能更容易在HIV/HCV感染者中检测到。 合并感染的患者，对他们来说，增加的免疫激活和炎症可能会导致持久的损害。的 拟议的研究将包括北方加州凯萨医疗机构成员的队列研究。 这一设置的优势包括380万成员的多样性和普遍性，内部 HCV和HIV单一感染的对照组，用于识别关键风险的电子健康记录（EHR） 因素和传染病登记处，以高质量地确定HCV和HIV病例。具体 目的是1）确定早期与延迟HCV治疗对肝和肝外的影响， HCV单一感染和HIV/HCV合并感染患者的结局; 2）评估肝脏和肝脏疾病的风险， HCV单一感染和HIV/HCV合并感染患者治疗后的肝外转归， 无HCV感染的HIV患者的匹配组;和3）确定HCV的成本-效果 治疗所有HCV单一感染和HIV/HCV合并感染的患者相比， 肝脏疾病的后期阶段。该职业发展奖将提供1）HCV和HIV/HCV方面的培训 流行病学，治疗和结果; 2）利用EHR进行传染病研究; 3）先进的 因果推理方法; 4）成本效益分析。这种指导性的研究和培训将直接 告知HCV患者的临床护理，并建立我作为该领域独立研究人员的职业生涯。

PROJECT SUMMARY/ABSTRACT This K01 award will provide the training and mentored research experience needed for me to become an independent researcher with a focus on improving the health outcomes of patients with or at risk for chronic viral infections. Chronic hepatitis C virus (HCV) infection affects over 3 million people in the U.S., with 80,000 HCV-related deaths per year. The health impacts of HCV are more severe in human immunodeficiency virus (HIV) patients, in whom HCV-associated liver disease is the leading cause of non-AIDS-related death. HIV/HCV coinfection has also been linked to an increased risk of extrahepatic outcomes, including cardiovascular and kidney disease. With the emergence of interferon-free regimens, most HCV patients can now be cured, regardless of HIV status. However, critical questions remain about 1) the effect of the timing of HCV treatment on hepatic and extrahepatic outcomes, 2) the ongoing risk of hepatic and extrahepatic outcomes after HCV cure, and 3) whether the clinical benefits of HCV treatment in early stages of liver disease warrant the use of costly new regimens in these patients. The high-risk population of HIV/HCV-coinfected patients is ideal for investigating these questions for two reasons. First, because HIV/HCV-coinfected patients are a priority group for HCV treatment, they will have received treatment over a range of liver disease stages, offering a unique opportunity to investigate the clinical and economic impacts of HCV treatment decisions. Second, ongoing risk of HCV-related outcomes after HCV cure may be more readily detectable in HIV/HCV- coinfected patients, for whom increased immune activation and inflammation may cause lasting damage. The proposed research will consist of cohort studies among members of Kaiser Permanente Northern California. The strengths of this setting include a diverse and generalizable population of 3.8 million members, internal HCV- and HIV-monoinfected comparison groups, an electronic health record (EHR) for identification of key risk factors, and infectious disease registries for high-quality ascertainment of HCV and HIV cases. The specific aims are to 1) determine the effect of early versus deferred HCV treatment on hepatic and extrahepatic outcomes among HCV-monoinfected and HIV/HCV-coinfected patients; 2) evaluate the risk of hepatic and extrahepatic outcomes among HCV-monoinfected and HIV/HCV-coinfected patients after HCV cure, and in a matched group of HIV patients without HCV infection; and 3) determine the cost-effectiveness of HCV treatment for all HCV-monoinfected and HIV/HCV-coinfected patients compared with deferral of treatment to later stages of liver disease. This career development award will provide training in 1) HCV and HIV/HCV epidemiology, treatment, and outcomes; 2) leveraging the EHR for infectious disease research; 3) advanced causal inference methods; and 4) cost-effectiveness analysis. This mentored research and training will directly inform the clinical care of HCV patients and establish my career as an independent researcher in the field.