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

项目摘要/摘要 这一K01奖项将为我提供成为一名 独立研究人员，专注于改善慢性病患者或有慢性病风险的患者的健康结果 病毒感染。慢性丙型肝炎病毒感染在美国影响着300多万人，其中8万人 每年与丙型肝炎病毒相关的死亡人数。丙型肝炎病毒对健康的影响在人类免疫缺陷病毒中更为严重 (艾滋病毒)患者，其中丙型肝炎相关肝病是非艾滋病相关死亡的主要原因。 艾滋病毒/丙型肝炎病毒混合感染也与肝外结局的风险增加有关，包括 心血管和肾脏疾病。随着无干扰素疗法的出现，大多数丙型肝炎患者可以 现在可以治愈了，无论艾滋病毒状态如何。然而，关键的问题仍然是1)时机的影响 丙型肝炎病毒治疗对肝和肝外结局的影响，2)肝和肝外的持续风险 丙型肝炎治愈后的结果，以及3)在肝病早期治疗丙型肝炎是否有临床益处 有理由在这些患者身上使用昂贵的新疗法。HIV/丙型肝炎病毒混合感染的高危人群 Patients是研究这些问题的理想选择，原因有两个。首先，因为艾滋病毒/丙型肝炎病毒混合感染的患者 是丙型肝炎病毒治疗的优先群体，他们将接受一系列肝病阶段的治疗， 为研究丙型肝炎病毒治疗决策的临床和经济影响提供了一个独特的机会。 其次，丙型肝炎治愈后与丙型肝炎病毒相关结果的持续风险可能更容易在艾滋病毒/丙型肝炎病毒中检测到。 合并感染的患者，对他们来说，免疫激活和炎症可能会造成持久的损害。这个 拟议的研究将包括对北加州Kaiser Permanente成员的队列研究。 这一环境的优势包括多样化和可推广的380万成员人口，内部 单一感染丙型肝炎病毒和艾滋病病毒的对照组，用于识别关键风险的电子健康记录(EHR) 因素，以及高质量确定丙型肝炎病毒和艾滋病毒病例的传染病登记。具体的 目的是：1)确定早期和延迟治疗丙型肝炎病毒对肝脏和肝外的影响 丙型肝炎病毒单一感染和HIV/丙型肝炎病毒混合感染患者的预后；2)评估肝脏和 丙型肝炎病毒单一感染患者和HIV/丙型肝炎病毒混合感染患者在丙型肝炎治愈后的肝外结局，以及在 无丙型肝炎病毒感染的HIV患者的匹配组；3)确定丙型肝炎病毒的成本-效果 对所有丙型肝炎病毒单一感染和艾滋病毒/丙型肝炎混合感染患者的治疗与推迟治疗的比较 肝病的晚期。该职业发展奖将提供1)丙型肝炎病毒和艾滋病毒/丙型肝炎病毒的培训 流行病学、治疗和结果；2)利用EHR进行传染病研究；3)高级 因果推理方法；4)成本-效果分析。这一指导研究和培训将直接 告知丙型肝炎患者的临床护理，并建立我作为该领域独立研究员的职业生涯。

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.