Disparities in Immune Fitness in HIV+ Subjects with Aging

HIV 受试者的免疫适应度随年龄增长的差异

• 批准号: 9203464
• 负责人: JANKO Z. NIKOLICH
• 金额: $ 18.6万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9203464
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Age; Aging; American; Anti-Retroviral Agents; Antibodies; Antibody Formation; Cardiovascular system; Caucasians; Cell Count; Chronic Disease; Cognitive; Comorbidity; Cytomegalovirus; Cytomegalovirus Infections; Data; Defect; Detection; Education; Elderly; Ethnic Origin; Exhibits; Fatty acid glycerol esters; Fibrinogen; Foundations; Functional disorder; Future; Gender; Goals; HIV; HIV Infections; HIV diagnosis; HLA-DR Antigens; Health; Hepatic; Herpesviridae; Hispanic Americans; Hispanics; Homeostasis; Immune; Immune response; Immunoglobulin G; Individual; Inflammation; Inflammatory; Influenza vaccination; Interferon Type II; Interferons; Interleukin-10; Interleukin-15; Interleukin-6; Latent Virus; Lead; Life; Measures; Memory; Metabolic Diseases; Metabolic syndrome; Molecular; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Pathway interactions; Patients; Peptides; Pericardial body location; Persons; Phenotype; Population; Premature aging syndrome; Recruitment Activity; Serum; T-Lymphocyte; TNF gene; Testing; Urine; Ursidae Family; Vaccinated; Variant; Viral; Viremia; Virus; Visceral; age related; aged; antiretroviral therapy; cohort; cytokine; ethnic disparity; exhaustion; experience; fitness; immune function; inflammatory marker; male; mortality; premature; research study; response; seroconversion; seropositive; trivalent influenza vaccine

HIV has become a chronic disease in the US due to efficient virus control by antiretroviral therapy (ART). With that, the population over age 50 with controlled HIV is growing and already numbers >600,000 people in the US. With age these individuals experience multiple comorbidities that appear independent of HIV itself, and anecdotally some of the pathophysiology in HIV+ individuals appears as pronounced/accelerated aging. Inflammation and a decline in immune function accompany both HIV and aging, suggesting that both could potentiate and/or drive aspects of exacerbated aging in people with HIV. Persistent cytomegalovirus (CMV) infection was implicated in immune aging and age-related inflammation too, but there are significant individual variations and an incomplete understanding on how CMV is controlled with aging. Limited data suggests that the premature “aging” phenotype seen in HIV+ patients is only found in those co-infected with CMV, but the control of CMV in HIV+ subjects, particularly those over 50, remains poorly understood. Hispanic Americans experience a disproportional number of HIV infections and are also likely to acquire CMV earlier and at higher rate compared to non-Hispanic Americans. With the Hispanics bearing a large HIV and CMV burden, it is critical to understand how ethnicity affects aging with HIV and CMV. To that effect, this exploratory proposal seeks to establish whether HIV+ Hispanic Americans (HIV+HA) exhibit different (increased) systemic inflammation (cytokines and inflammatory markers) and reduced adaptive immune fitness (homeostasis at baseline and response to CMV and influenza vaccination) compared to HIV+ non-Hispanics (HIV+nHA) in the course of aging. The Aims will ask: SA1. Is Hispanic ethnicity in HIV+ subjects associated with accentuated inflammation and pronounced defects of immune homeostasis in aging? SA2. Do ethnic disparities in HIV+ subjects critically modulate immune response fitness with aging? The above experiments will provide a hypothesis-generating foundation for larger mechanistic studies of cellular and molecular inflammatory and immune pathways that may explain how Hispanic Americans handle immune aging with HIV.

由于抗逆转录病毒疗法对病毒的有效控制，艾滋病毒在美国已成为一种慢性疾病 （ART）。因此，50岁以上的艾滋病毒控制人口正在增长， 在美国有超过60万人。随着年龄的增长，这些人会出现多种合并症， 独立于艾滋病毒本身，并且据传闻，艾滋病毒+个体的一些病理生理学表现为 明显/加速老化。炎症和免疫功能下降伴随着艾滋病毒和 衰老，这表明两者都可能增强和/或推动患有 艾滋病。持续性巨细胞病毒（CMV）感染与免疫衰老和年龄相关性 炎症，但有显着的个体差异和不完整的理解如何 CMV随着年龄的增长而得到控制。有限的数据表明，在HIV+中观察到的过早“衰老”表型 仅在合并CMV感染的患者中发现，但在HIV+受试者中， 50岁以上的人，仍然知之甚少。 西班牙裔美国人感染艾滋病毒的人数不成比例， 与非西班牙裔美国人相比，他们更早获得CMV，并且发病率更高。随着西班牙裔轴承 作为一个巨大的艾滋病毒和巨细胞病毒负担，了解种族如何影响艾滋病毒和巨细胞病毒的衰老至关重要。 为此，这项探索性的提案旨在确定艾滋病毒+西班牙裔美国人是否 (HIV+HA）表现出不同的（增加的）全身性炎症（细胞因子和炎性标志物）， 适应性免疫适应性降低（基线稳态和对CMV和流感的应答 在老化过程中，与HIV+非西班牙裔人（HIV+nHA）相比，目标会问： SA 1. HIV+受试者中的西班牙裔是否与炎症加重相关， 衰老过程中免疫稳态的明显缺陷 SA 2. HIV+受试者的种族差异是否严重调节免疫反应适应性 随着年龄的？ 上述实验将为更大规模的机理研究提供一个产生假说的基础 细胞和分子炎症和免疫途径的研究，可以解释如何西班牙裔 美国人用艾滋病毒处理免疫衰老。