Disparities in Immune Fitness in HIV+ Subjects with Aging

由于抗逆转录病毒疗法有效地控制了病毒，艾滋病毒在美国已成为一种慢性病 (艺术)。因此，50岁以上的艾滋病毒携带者人数正在增长，而且已经达到了 &gt；在美国有60万人。随着年龄的增长，这些人会出现多种合并症 与HIV本身无关，而且坊间传闻HIV+个体的一些病理生理学表现为 明显的/加速老化的炎症和免疫功能下降都伴随着HIV和 衰老，这表明两者都可以加强和/或推动老年人衰老加剧的方面 爱滋病毒。持续巨细胞病毒(CMV)感染与免疫衰老和年龄相关 炎症也是如此，但有显著的个体差异和对其原因的不完全理解 CMV随老化而受到控制。有限的数据表明，HIV+中出现的早衰表型 仅在合并感染CMV的患者中发现CMV，但在HIV+人群中CMV的控制，尤其是 人们对50岁以上的人仍然知之甚少。 拉美裔美国人感染艾滋病毒的人数不成比例，也有可能 与非西班牙裔美国人相比，获得CMV的时间更早，速度更快。带着拉美裔的气质 作为一种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感染的老龄化至关重要。 为此，这项探索性的提案试图确定艾滋病毒+拉美裔美国人 (HIV+HA)表现出不同(增加)的全身炎症(细胞因子和炎症标志物)和 适应性免疫适应性降低(基线的动态平衡以及对巨细胞病毒和流感的反应 在老龄化过程中，与艾滋病毒+非西班牙裔(艾滋病毒+非西班牙裔)相比，艾滋病毒+非西班牙裔(艾滋病毒+非西班牙裔)的儿童(艾滋病毒+非西班牙裔)更容易接受疫苗接种。AIMS将提出以下问题： SA1.HIV+受试者中的西班牙裔种族是否与加重的炎症和 衰老过程中免疫动态平衡的显著缺陷？ SA2.HIV阳性受试者的种族差异是否对免疫反应的适合性起关键作用 随着年龄的增长？ 上述实验将为更大的机构学提供假说生成的基础 对细胞和分子炎症和免疫途径的研究可能解释西班牙裔 美国人通过艾滋病毒应对免疫衰老。

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.