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

 描述（由申请人提供）：美国艾滋病毒感染者（PLWH）的人口正在老龄化;预计到2015年，美国一半以上的PLWH将超过50岁。心脏，肺和血液疾病在老年PLWH中很常见，可能是由于HIV感染本身及其导致的炎症，抗逆转录病毒治疗及其毒性，病毒合并感染，其他共病状况，传统风险因素如烟草，以及其他行为如物质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（VTE）和慢性贫血的患病率和发病率增加相关的风险因素，并确定与这些疾病不良结局相关的风险因素。了解多种因素对疾病风险增加的贡献对于制定策略以改善PLWH中这些主要心脏，肺部和血液疾病的预防，诊断和治疗至关重要。该应用程序利用了来自艾滋病研究中心综合临床系统网络（CNICS）的综合临床数据和生物储存库样本，这是RFA中特别建议的数据源。这个大型、多样化、特征良好的多中心队列采集了纵向临床数据、患者报告的结果（如体力活动和物质使用）以及生物标本，有助于采用细致入微的方法来解决风险。此外，CNICS基础设施允许对结局进行仔细审查和确认，捕获关键区别，如MI类型（STEMI与非STEMI）和DVT位置。我们的多学科团队是唯一准备利用这些资源，以解决重要的差距，在理解的病理生理学，诊断，治疗和影响MI，COPD，VTE和贫血在PLWH追求3个目标。目的1是确定PLWH中MI、COPD、VTE和贫血的患病率和发病率，以及其传统和HIV特异性危险因素。目的2是确定PLWH中这四种情况的并发症和不良结局的风险因素。具体结果将包括死亡率、多种发病率、健康相关生活质量、虚弱和多种用药。目的3是确定PLWH中MI、COPD、VTE和贫血的免疫学预测因子，重点关注炎症、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，并将大大提高对PLWH心脏，肺部和血液疾病机制的理解，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.