Early Senescence in HIV disease: When Race defines Age

项目总结(见说明)： 自认识到艾滋病毒大流行以来的25年多时间里，由于抗逆转录病毒治疗的改进，艾滋病毒感染者已迈向高龄。尽管病毒受到抑制，但非艾滋病定义的并存疾病，如动脉粥样硬化、神经认知能力下降和骨质疏松症仍会发生，呈现出与老年有趣的相似之处。高效抗逆转录病毒疗法(HAART)在过去十年中降低了死亡率，尽管与西班牙裔、亚洲人或白人相比，感染艾滋病毒的非裔美国人的死亡率更高。尽管这种差异的原因尚不清楚，但心理社会压力可能是导致非裔美国人艾滋病病毒感染者的临床结果比白人更差的一个因素。这项提案的目标是测试一种假设，即艾滋病毒感染者中的免疫扰动，即免疫激活和炎症，将有助于早期免疫衰老，并且与白人艾滋病毒感染者相比，这些扰动在非裔美国人中得到加强，从而导致过早衰老和更快的艾滋病毒疾病进展。该项目还将测试这一假设，即心理社会压力可能导致非裔美国人比白人艾滋病毒感染者更活跃、炎症和衰老，以及更快的疾病进展。 我们将在研究核心的Rush CEDHA储存库的标本中进行这项研究。对于这一应用，我们将研究先天免疫激活是否有助于免疫衰老，并使用端粒缩短作为衰老的衡量标准。我们将评估年龄匹配的HIV感染者和未感染者(50-60岁)和老年未感染者(AGE&GT；70)的免疫扰动、免疫激活(CD4和CDS T细胞上的HLADR+CD38+表达)、天然细胞激活(可溶性CD14、1型干扰素-α和β)、炎症(支持和抗)肿瘤坏死因子-α、IL-6、IL-10)和免疫衰老(定义为CD28-CD57+在CD4和CDS T细胞上的表达和端粒长度)。将在HIV感染者中评估种族和心理社会压力对免疫紊乱的影响。该项目拥有跨学科的专业知识，来自艾滋病毒/艾滋病领域的主要临床医生、免疫学家、神经心理学家和生物统计学家，以成功地实施这项研究的目的和目标。

PROJECT SUMMARY (See instructions): Over 25 years since recognition of the HIV pandemic, the HIV-infected subjects have moved toward older ages due to improvements in antiretroviral therapy. Non-AIDS-defining co-morbidities such as atherosclerosis, neurocognitive decline and osteoporosis occur despite viral suppression, presenting intriguing similarities to old age. Highly active anti-retroviral therapy (HAART) has reduced mortality in the last decade though mortality rate in HIV-infected African Americans is higher as compared to Hispanic, Asians or whites. Although the reasons for the disparities are poorly understood, psychosocial stress is one factor that may account for the poorer clinical outcomes in HIV-infected subjects in African Americans compared to Whites. The goal of this proposal is to test the hypothesis that immune perturbations, namely immune activation and inflammation, in HIV-infected subjects will contribute to early immune senescence and that these perturbations are enhanced in African Americans compared to white HIV-infected subjects contributing to early senescence and faster HIV disease progression. This project will also test the hypothesis that psychosocial stress may account for the increased activation, inflammation and senescence in African Americans compared to white HIV infected subjects as well as more rapid disease progression. We will conduct this study in specimens from the Rush CEDHA Repository of the Research Core. Novel to this application we will study whether innate immune activation contributes to immune senescence and use telomere shortening as a measure of senescence. We will evaluate immune perturbations, immune activation (HLADR+ CD38+ expression on CD4 and CDS T cells), innate cell activation (soluble CD14, type 1 intereferon-alpha and beta), inflammation (pro- and anti) TNF-alpha, IL-6, IL-10) and immune senescence (defined as CD28-CD57+ expression on CD4 and CDS T cells and telomere length) in age matched HIV infected and uninfected individuals (age 50-60) and older HIV-uninfected (age >70), a unique population accessible via the Research Core of Rush CEDHA. Impact of race and psychosocial stress on immune perturbation will be evaluated in HIV infected subjects. This project has a cross discipline expertise, from leading clinicians in the HIV/AIDS field, immunologists, neuropsychologist and bio-statiscian for successful implementation of the aims and objectives of this study.