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

项目总结 在美国，老年艾滋病毒携带者(PWH)是一个迅速扩大的群体，患上 尽管病毒学受到抑制，但认知障碍。虽然认知功能下降是导致 生活质量下降，目前影响20-50%的PWH，没有有效的诊断或治疗方法 预测和跟踪疾病的进展，并减少有认知障碍的重症肝炎患者的发病率 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照顾感染艾滋病毒的老龄化人口， 我们认识到有必要进行微创诊断，如血液生物标志物，以评估认知能力 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记物有望 成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中的诊断作用 大量老年PWH患者接受抗逆转录病毒治疗至关重要。 在家长R01(R01AG069575)中，Pi(Emily Hyle博士)和研究团队详细说明了开发方法 并为老龄化的艾滋病毒人群建立了痴呆症和多发病的模拟模型， (认知障碍、艾滋病毒、衰老、心脏、心理健康和痴呆症)模型。在这个管理部门中 作为补充，研究小组将利用艾滋病临床试验小组(ACTG)的数据和样本 两种血浆标志物神经丝光蛋白(NFL)和胶质纤维酸性蛋白的能力研究 (GFAP)，以区分接受抗逆转录病毒治疗的老年PWH(超过45岁) 认知障碍和那些没有认知障碍的人。这些生物标记物是 神经轴突损伤和星形胶质细胞增殖，并正在积极调查其他 神经障碍，包括没有艾滋病毒的老年人的认知能力下降，出现在记忆诊所。至 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，确定与认知功能和认知功能相关的常见并发症之间的关系 抗逆转录病毒治疗时PWH患者这些生物标志物的血浆浓度。由此生成的数据 提案将被用来扩展魅力模型；然后研究团队将使用魅力模型 评估这两个生物标志物的测试特征范围的含义并检查其影响 以及基于人们每次测试的成本范围的生物标记物诊断方法的成本效益 因感染艾滋病毒而变老。

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.