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.

项目概要 在美国，老年艾滋病毒感染者 (PWH) 是一个迅速扩大的群体，并且感染艾滋病毒的风险不断增加 尽管病毒学受到抑制，但仍存在认知障碍。虽然认知功能下降是导致 生活质量下降，目前影响 20-50% 的感染者，目前尚无有效的诊断或治疗方法 预测和跟踪疾病进展并降低患有认知障碍的感染者的发病率 抗逆转录病毒治疗。随着越来越多的艾滋病毒和初级保健诊所的提供者为感染艾滋病毒的老龄化人口提供护理， 我们认识到需要微创诊断，例如基于血液的生物标记物来评估认知能力 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有望 作为记忆诊所诊断工具库的一部分在临床上可用。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 对大量老年感染者进行抗逆转录病毒治疗至关重要。 在母体 R01 (R01AG069575) 中，PI (Emily Hyle 博士) 和研究团队详细介绍了开发方法 并为老龄化的艾滋病毒人群建立了痴呆症和多重发病的模拟模型，CHARMED （认知障碍、艾滋病毒、衰老、心脏、心理健康和痴呆）模型。在本行政 作为补充，研究小组将利用艾滋病临床试验组（ACTG）的数据和样本来 研究两种血浆生物标志物、神经丝光 (NfL) 和胶质纤维酸性蛋白的能力 (GFAP)，以区分接受抗逆转录病毒治疗的老年 PWH（45 岁以上） 认知障碍和没有认知障碍的人。这些生物标志物可以替代 神经轴突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，包括在记忆诊所就诊的未感染艾滋病毒的老年人的认知能力下降。到 为临床解释提供更准确的血浆 NfL 和 GFAP 水平估计，该团队将 另外确定经常与认知功能相关的合并症和 接受抗逆转录病毒治疗的感染者中这些生物标志物的血浆浓度。由此产生的数据 提案将用于扩展CHARMED模型；研究团队随后将使用 CHARMED 模型 评估测试特征范围对这两种生物标志物的影响并检查其影响 以及基于人群每次测试的一系列成本的生物标记诊断方法的成本效益 感染艾滋病毒而衰老。