Cardiovascular, Pulmonary and Hematological Disease in HIV: Prevention and Treatment

 描述(由申请人提供)：美国艾滋病毒携带者(PLWH)的人口正在老龄化；预计到2015年，超过一半的美国PLWH将超过50岁。心、肺和血液疾病在老年PLWH中很常见，可能是由于艾滋病毒感染本身和由此导致的炎症、抗逆转录病毒治疗及其毒性、病毒合并感染、其他共病条件、传统危险因素(如烟草)和其他行为(如药物使用)的复杂相互作用。我们建议严格评估与PLWH中心肌梗死(MI)、慢性阻塞性肺疾病(COPD)、静脉血栓栓塞症(VTE)和慢性贫血的患病率和发病率增加相关的危险因素，并从这些情况确定与不良预后相关的危险因素。了解多种因素对疾病风险增加的影响，对于制定策略以改进PLWH中这些主要心、肺和血液疾病的预防、诊断和治疗至关重要。这一应用程序利用了来自艾滋病研究中心综合临床系统研究网络(CNICs)的全面临床数据和生物信息库样本，这是RFA特别建议的数据源。这一大型、多样化、特征良好的多部位队列收集了纵向临床数据、患者报告的结果，如体力活动和物质使用，以及促进微妙和详细的方法来应对风险的生物标本。此外，CNICS基础设施允许仔细审查和验证结果，以捕捉诸如MI类型(STEMI与非STEMI)和DVT位置等关键区别。我们的多学科团队独一无二地准备利用这些资源，通过追求三个目标来解决在了解MI、COPD、VTE和贫血对PLWH的病理生理学、诊断、治疗和影响方面的重要差距。目的1是确定PLWH中MI、COPD、VTE和贫血的患病率和发生率，以及它们的传统和HIV特有的危险因素。目的2是确定导致PLWH并发症和预后不良的危险因素。具体结果将包括死亡率、多种发病率、与健康相关的生活质量、虚弱和多药并存。目的3是确定PLWH中MI、COPD、VTE和贫血的免疫学预测因素，重点是炎症、凝血、单核细胞活化和肠上皮完整性的可溶性标志物。这些研究可以确定治疗干预的新靶点。从这些研究中获得的新知识将为临床决策提供信息，并将极大地提高对PLWH中心、肺和血液疾病机制的了解，这反过来将促进合理和有针对性的治疗方法的发展，以改善结果。

 DESCRIPTION (provided by applicant): The population of people living with HIV (PLWH) in the US are aging; it is projected that by 2015 more than half of US PLWH will be over age 50. Heart, lung, and blood diseases are common among aging PLWH, likely due to a complex interplay of HIV infection itself and resulting inflammation, antiretroviral treatments and their toxicities, viral co-infections, other co-morbid conditions, traditional risk factors such as tobaco, and other behaviors such as substance use. We propose to rigorously assess risk factors associated with increased prevalence and incidence of myocardial infarction (MI), chronic obstructive pulmonary disease (COPD), venous thromboembolism (VTE), and chronic anemia among PLWH, and to determine risk factors associated with poor outcomes from these conditions. Understanding the contribution of multiple factors to the increased risk of disease is crucial to developing strategies to improve prevention, diagnosis, and treatment of these major heart, lung and blood diseases in PLWH. This application leverages comprehensive clinical data and biorepository samples from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a data source specifically suggested in the RFA. This large, diverse, well-characterized multi-site cohort captures longitudinal clinical data, patient reported outcomes such as physical activity and substance use, and biospecimens facilitating a nuanced and detailed approach to addressing risk. In addition, CNICS infrastructure allows outcomes to be carefully reviewed and validated capturing key distinctions such as MI type (STEMI vs. non-STEMI) and DVT location. Our multidisciplinary team is uniquely poised to leverage these resources to address important gaps in understanding the pathophysiology, diagnosis, treatment, and impact of MI, COPD, VTE and anemia in PLWH by pursuing 3 aims. Aim 1 is to determine the prevalence and incidence of MI, COPD, VTE and anemia in PLWH, as well as their traditional and HIV-specific risk factors. Aim 2 is to determine risk factors for complicatios and poor outcomes from these four conditions in PLWH. Specific outcomes will include mortality, multi-morbidity, health-related quality of life, frailty, and polypharmacy. Aim 3 is to determine immunologic predictors of MI, COPD, VTE and anemia among PLWH, focusing on soluble markers of inflammation, coagulation, monocyte activation, and gut epithelial integrity. These investigations can identify novel targets for therapeutic interventions. New knowledge gained from these investigations will inform clinical decision making and will dramatically improve understanding of the mechanisms of heart, lung, and blood diseases in PLWH, which in turn will enhance the development of rational and targeted therapeutic approaches to improve outcomes.