Clinical and Translational Research Support Core for Institution # 269291

总结 目前的人类免疫缺陷病毒1型（HIV-1）大流行是艾滋病毒感染者（PWH） 通过长期治疗，感染得到了很好的抑制。这引导了研究 关注（i）合并症（衰老、心血管、癌症、代谢和免疫激活），（ii）副作用 抗逆转录病毒治疗（ART），（iii）神经认知和行为障碍（发生约40%的 时间），（iv）NeuroHIV差异的社会和结构决定因素，以及（v）新的治疗方法和治愈方法 战略布局所有这些地区都依赖于从威尔斯亲王医院获取相关样本。鉴于这些高- 研究的优先领域，临床和转化研究支持核心（CTRSC），由Wigdahl博士领导， 将招募参与者（白色、黑人、西班牙裔和相应的 未感染的参与者队列），以继续开发丰富且管理良好的临床人群， 可以提供数据、建议、技术专长和试剂来解决这些问题。的一个主要 该中心的研究主题集中在潜伏期，水库和治疗策略，包括水库，如 中枢神经系统（CNS）。因此，迫切需要了解病毒储存库的遗传学 和艾滋病毒-1准种的遗传性质的个人很好地抑制抗逆转录病毒疗法。 也将进行了解免疫反应在威尔斯亲王经历老化过程，以及 其他合并症，包括药物滥用。此外，纵向样本来自 神经心理学特征良好的PWH将有助于涉及生物标志物的纵向研究， neuroHIV潜在的免疫因素。CTRSC将通过以下方式实现这些目标：（1）细化和利用 临床队列的研究，以检查HIV-1疾病的参数和许多共病因素（Szep/Pirrone）， (2)利用全面的神经心理学评估来表征性质，进展， HIV-1中神经认知障碍的相关性（Schultheis/Devlin），以及（3）病毒学和 免疫学参数（Nonnemacher/ Haddad）。CTRSC将与中央行政部门 和管理核心（CAMC），并将在目标1和2与NeuroHIV和社区密切合作 伙伴关系和差异核心（NHCPDC）。它将使用病毒基因编辑和生物信息学核心（VGEBC） 用于下一代测序服务的实验设计和信息支持（目标1和3）， 细胞生物学和功能分析核心（CBFAC），以帮助开发细胞系，分离和开发原代 细胞群（目标3）。最后，CTRSC将与早期职业和已建立的研究者互动， 在艾滋病毒社区内外开发新的研究问题和赠款使用发展 和研究导师核心（DRMC），并提供科学指导，在发现，翻译/临床， 或神经HIV的行为/神经心理学方面。服务将在德崇公司内部广泛宣传 和圣殿，以及在校外。

SUMMARY The current human immunodeficiency virus type 1 (HIV-1) pandemic is one where people living with HIV (PWH) have had well-suppressed infection with therapy for prolonged periods of time. This has guided research towards focusing on (i) comorbidities (aging, cardiovascular, cancer, metabolic, and immune activation), (ii) side effects of antiretroviral therapy (ART), (iii) neurocognitive and behavioral disorders (occurs approximately 40% of the time), (iv) social and structural determinants of NeuroHIV disparities, and (v) new therapeutics and cure strategies. All of these areas rely on access to PWH and associated samples from PWH. Given these high- priority areas of research, the Clinical and Translational Research Support Core (CTRSC), led by Dr. Wigdahl, will have as its main SERVICE OBJECTIVE to enroll participants (White, Black, Hispanic and corresponding uninfected participant cohorts) to continue the development of a rich and well-managed clinical population that can provide data, advice, technical expertise, and reagents to address many of these questions. One of the main research themes of this center focuses on latency, reservoirs, and cure strategies including reservoirs like the central nervous system (CNS). As such, there is a pressing need to understand the genetics of the viral reservoir and the genetic nature of the HIV-1 quasispecies in individuals well-suppressed by ART. Immunophenotyping will also be performed to understand the immune response in PWH experiencing the aging process as well as other comorbid conditions including substance abuse. In addition, having longitudinal samples from neuropsychologically well-characterized PWH will facilitate longitudinal investigations involving biomarkers and immune factors underlying neuroHIV. The CTRSC will accomplish these goals by (1) refinement and utilization of the clinical cohort to examine parameters of HIV-1 disease and a number of comorbid factors (Szep/Pirrone), (2) utilizing comprehensive neuropsychological evaluation to characterize the nature, progression, and correlates of neurocognitive impairment in HIV-1 (Schultheis/Devlin), and (3) characterization of virological and immunological parameters (Nonnemacher/ Haddad). The CTRSC will interface with the Central Administrative and Management Core (CAMC) and will work closely in Aims 1 and 2 with the NeuroHIV and Community Partnership and Disparities Core (NHCPDC). It will use the Viral Gene Editing and Bioinformatics Core (VGEBC) for experimental design and informatic support of next-generation sequencing services (Aims 1 and 3) and the Cell Biology and Functional Analyses Core (CBFAC) to help develop cell lines and isolate and develop primary cell populations (Aim 3). Finally, the CTRSC will interact with early-career and established investigators from within and outside the HIV community to develop new research questions and grants using the Developmental and Research Mentorship Core (DRMC) and by providing scientific guidance in discovery, translational/clinical, or behavioral/neuropsychological aspects of neuroHIV. Services will be advertised broadly internally at Drexel and Temple and extramurally.