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

在新的 HCV 治疗时代优化 HIV/HCV 合并感染患者的护理

• 批准号: 9393181
• 负责人: Julia L. Marcus
• 金额: $ 12.02万
• 依托单位: HARVARD PILGRIM HEALTH CARE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9393181
• 关键词: Optimizing; Care; HIV; HCV; Coinfected

 DESCRIPTION (provided by applicant): 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 an estimated 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 HCV-related outcomes and 2) ongoing risk for HCV-related outcomes after HCV cure. This proposal addresses these pressing clinical questions with a focus on HIV/HCV-coinfected 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 been treated over a range of liver disease stages, offering a unique opportunity to investigate the risks of treatment deferral. Second, ongoing risk of HCV-related outcomes after HCV cure may be more readily detectable in HIV/HCV- coinfected patients, who may experience lasting damage from increased immune activation and inflammation during HIV/HCV coinfection. 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 3.3 million members, internal HCV-monoinfected and HIV-monoinfected comparison groups, and extensive clinical data from an electronic health record. The specific aims are to 1) determine the effect of early versus deferred HCV treatment on hepatic and extrahepatic outcomes among HIV/HCV-coinfected and HCV-monoinfected patients, and 2) evaluate the risk of hepatic and extrahepatic outcomes among HIV/HCV-coinfected and HCV-monoinfected patients after HCV cure, and in a matched group of HIV patients who never had HCV infection. The proposed research will be strengthened by the use of methods such as marginal structural models that overcome limitations of standard approaches. This career development award will provide training in the following areas: 1) epidemiology and pathogenesis of HCV infection and HIV/HCV coinfection, 2) HIV and liver- related outcomes, 3) clinical management of HCV and HIV/HCV patients, and 4) advanced biostatistical methods with an emphasis on causal inference. This mentored research and training will directly inform the clinical care of HIV/HCV patients and establish my career as an independent researcher in the field.

 描述（由适用提供）：该K01奖将为我提供成为独立研究人员所需的培训和修补研究经验，重点是改善患有或面临慢性病毒感染风险的患者的健康结果。慢性丙型肝炎病毒（HCV）感染影响了美国超过300万人，估计每年有80,000例HCV相关的死亡。 HCV的健康影响在人类免疫缺陷病毒（HIV）患者中更为严重，其中与HCV相关的肝病是与非AID相关死亡的主要原因。 HIV/HCV共感染也与增加肝外结局的风险增加有关，包括心血管疾病和肾脏疾病。随着无干扰方案的出现，无论艾滋病毒状况如何，大多数HCV患者现在都可以治愈。但是，关键问题仍然是1）HCV治疗时间对HCV相关结果的影响以及2）HCV治疗后与HCV相关结果的持续风险。该提案以HIV/HCV可感染的患者为重点解决了这些紧迫的临床问题。 HIV/HCV-共感染患者的高风险人群非常适合研究这些患者 问题有两个原因。首先，由于HIV/HCV-共感染患者是HCV治疗的优先组，因此他们将在一系列现场疾病阶段接受治疗，为研究治疗延期的风险提供独特的机会。其次，在HIV/HCV-共感染的患者中，HCV治疗后与HCV相关结果的持续风险可能更容易检测到，他们在HIV/HCV共感染期间可能会因免疫激活和炎症增加而造成持久损害。拟议的研究将包括北加利福尼亚州Kaiser Permanente的成员的队列研究。这种环境的优势包括330万成员的潜水员和可推广人口，内部HCV - 单次感染和HIV - 单人感染的比较组，以及来自电子健康记录的大量临床数据。 The specific aims are to 1) determine the effect of early versus deferred HCV treatment on hepatitic and extrahepatitic outcomes among HIV/HCV-coinfected and HCV-monoinfected patients, and 2) evaluate the risk of hepatitic and extrahepatitic outcomes among HIV/HCV-coinfected and HCV-monoinfected patients after HCV cure, and in a matched group of从未感染HCV的HIV患者。拟议的研究将通过使用诸如克服标准方法局限性的边际结构模型之类的方法来加强。该职业发展奖将在以下领域提供培训：1）HCV感染和HIV/HCV共感染的流行病学和发病机理，2）2）HIV和与肝脏相关的结果，3）HCV和HIV/HCV患者的临床管理以及4）高级生物统计学方法，并具有紧急催化性催化性的促催化性。这项修改的研究和培训将直接为艾滋病毒/HCV患者的临床护理提供信息，并确立我作为该领域独立研究人员的职业。