Early Senescence in HIV disease: When Race defines Age

自认识到艾滋病毒大流行以来的25年多里，由于抗逆转录病毒疗法的改进，感染艾滋病毒的受试者已走向老年。非艾滋病定义的合并症，如动脉粥样硬化、神经认知能力下降和骨质疏松症，尽管病毒受到抑制，但仍会发生，与老年有有趣的相似之处。尽管感染艾滋病毒的非裔美国人的死亡率高于西班牙裔、亚洲人或白人，但在过去十年中，高效抗逆转录病毒疗法（HAART）降低了死亡率。尽管造成这种差异的原因尚不清楚，但社会心理压力可能是导致非裔美国人感染艾滋病毒的临床结果比白人差的一个因素。这一建议的目的是验证这样的假设，即免疫干扰，即免疫激活和炎症，在HIV感染的受试者中会导致早期免疫衰老，并且与白人HIV感染受试者相比，这些干扰在非裔美国人中会增强，从而导致早期衰老和更快的HIV疾病进展。该项目还将测试一个假设，即与感染艾滋病毒的白人受试者相比，社会心理压力可能导致非裔美国人的激活、炎症和衰老增加，以及疾病进展更快。

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.