The CHARMED model: a multimorbidity simulation model for people aging with HIV

CHARMED 模型：针对艾滋病毒老年患者的多发病模拟模型

• 批准号: 10613706
• 负责人: Emily Parker Hyle
• 金额: $ 42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613706
• 关键词: AIDS clinical trial group; Administrative Supplement; Affect; Age; Aging; Astrocytes; Astrocytosis; Biological Assay; Biological Markers; Blood; Brain Injuries; Cardiovascular Diseases; Caring; Cerebrospinal Fluid; Characteristics; Chronic Kidney Failure; Clinic; Clinical; Cognitive; Collection; Data; Dementia; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Education; Elderly; Enrollment; Glial Fibrillary Acidic Protein; Goals; HIV; HIV antiretroviral; Heart; Impaired cognition; Individual; Injury; Investigation; Kidney Diseases; Light; Manuscripts; Measures; Medical; Memory; Mental Health; Methods; Modeling; Morbidity - disease rate; Neuroglia; Neurologic; Neurons; Neuropathy; Neuropsychology; Outcome; Parents; Participant; Performance; Persons; Phenotype; Plasma; Plasma Proteins; Population; Positioning Attribute; Prevention; Primary Health Care; Prospective Studies; Proteins; Provider; Quality of life; Research; Research Personnel; Resolution; Risk; Risk Factors; Sampling; Surrogate Markers; Testing; Therapeutic; Time; United States; Use Effectiveness; aging population; antiretroviral therapy; base; blood-based biomarker; cognitive function; cognitive performance; cohort; comorbidity; cost; cost effectiveness; diagnostic tool; experience; improved; minimally invasive; models and simulation; multiple chronic conditions; nervous system disorder; neurofilament; neuroimaging; predictive marker; prognostic; protein function; screening; sex; tool

PROJECT SUMMARY Older people with HIV (PWH) in the United States are a rapidly expanding group and are at increased risk for cognitive impairment despite virologic suppression. While declining cognitive function is a critical contributor to reduced quality of life and currently affects 20-50% of PWH, there are no effective diagnostics or therapeutics to predict and track disease progression and to mitigate morbidity in PWH with cognitive impairment on antiretroviral therapy. As more providers in HIV and primary care clinics care for an aging population with HIV, we recognize the need for minimally-invasive diagnostics such as blood-based biomarkers to assess cognitive function. Blood-based biomarkers that can detect proteins produced by neurons or glial cells are poised to become clinically available as part of a repertoire of diagnostic tools in memory clinics. Assessing the diagnostic performance of these blood biomarkers in predicting cognitive impairment and its progression in large cohorts of older PWH on antiretroviral therapy is critically important. In the parent R01 (R01AG069575), the PI (Dr. Emily Hyle) and research team detailed methods for developing and populating a simulation model of dementia and multimorbidity for the aging HIV population, the CHARMED (Cognitive impairment, HIV, Aging, heaRt, MEntal health, and Dementia) model. In this administrative supplement, the research team will leverage data and samples from the AIDS Clinical Trials Group (ACTG) to investigate the ability of two plasma biomarkers, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), to discriminate between older PWH (over age 45 years) on antiretroviral therapy who develop cognitive impairment and those who remain free of cognitive impairment. These biomarkers are surrogates for neuroaxonal injury and astrocyte proliferation, respectively, and are actively under investigation for other neurological disorders, including cognitive decline in older people without HIV presenting to memory clinics. To provide more accurate estimates of plasma NfL and GFAP levels for clinical interpretations, the team will additionally determine the relationship between comorbidities frequently associated with cognitive function and plasma concentrations of these biomarkers in PWH on antiretroviral therapy. Data generated from this proposal will be used to expand the CHARMED model; the research team will then use the CHARMED model to assess the implications of the range of test characteristics for these two biomarkers and examine the impact and cost-effectiveness of a biomarker approach to diagnosis based on a range of costs per test among people aging with HIV.

项目摘要 在美国，患有艾滋病毒（PWH）的老年人是一个迅速扩大的群体，面临着增加的风险 尽管抑制了病毒，但认知障碍。虽然认知功能下降是对 降低生活质量，目前影响PWH的20-50％，没有有效的诊断或治疗学 预测和跟踪疾病进展并减轻PWH的发病率，并具有认知障碍 抗逆转录病毒疗法。随着艾滋病毒和初级保健诊所的越来越多的提供者护理艾滋病毒的老龄化， 我们认识到需要最小侵入性诊断，例如基于血液的生物标志物来评估认知 功能。可以检测神经元或神经胶质细胞产生的蛋白质的血液生物标志物已准备就绪 作为记忆诊所诊断工具曲目的一部分，可以在临床上使用。评估 这些血液生物标志物在预测认知障碍及其进展方面的诊断性能 抗逆转录病毒疗法上的大量较老的PWH至关重要。 在父r01（R01AG069575）中，PI（Emily Hyle博士）和研究团队详细介绍了开发的方法 并为衰老的艾滋病毒群体填充痴呆症和多种多发病模型， （认知障碍，艾滋病毒，衰老，心脏，心理健康和痴呆症）模型。在此管理中 补充，研究小组将利用AIDS临床试验组（ACTG）的数据和样本 研究两个血浆生物标志物，神经丝（NFL）和神经胶质原纤维酸性蛋白的能力 （GFAP），在抗逆转录病毒疗法上区分较老的PWH（45岁以上） 认知障碍和那些没有认知障碍的人。这些生物标志物是代孕 神经司长损伤和星形胶质细胞增殖，并正在积极研究其他 神经系统疾病，包括没有艾滋病毒的老年人的认知能力下降，向记忆诊所呈现。到 提供对血浆NFL和GFAP水平的更准确估计，以进行临床解释，团队将 另外，确定经常与认知功能相关的合并症和 这些生物标志物在抗逆转录病毒疗法上的这些生物标志物的血浆浓度。从中生成的数据 建议将用于扩展迷人的模型；然后，研究小组将使用迷人的模型 评估这两个生物标志物的测试特征范围的含义并检查影响 生物标志物方法的诊断方法的成本效益，该方法基于每次测试的一系列费用 艾滋病毒衰老。