Clinical and Translational Research Support Core for Institution # 269291

摘要 目前的人类免疫缺陷病毒1型(HIV-1)大流行是一种艾滋病毒携带者(PWH) 长期接受治疗，感染得到了很好的抑制。这将研究引向了 重点关注(I)合并症(衰老、心血管疾病、癌症、代谢和免疫激活)，(Ii)副作用 抗逆转录病毒疗法(ART)，(Iii)神经认知和行为障碍(约40%发生在 时间)、(4)神经艾滋病毒差异的社会和结构决定因素，以及(5)新的治疗方法和治疗方法 战略。所有这些地区都依赖威尔斯亲王医院和威尔斯亲王医院的相关样本。考虑到这些高- 优先研究领域，由Wigdahl博士领导的临床和转译研究支持核心(CTRSC)， 将以招募参与者(白人、黑人、西班牙裔和相应的 未感染的参与者队列)，以继续发展丰富和管理良好的临床人口 可以提供数据、建议、技术专长和试剂来解决其中许多问题。其中一个主要的 该中心的研究主题集中在潜伏期、存储库和治愈策略，包括像 中枢神经系统(CNS)。因此，迫切需要了解病毒库的遗传学。 以及被ART很好地抑制的个体中HIV-1准种的遗传性质。免疫表型 也将执行，以了解免疫反应在威尔斯亲王经历老化过程以及 包括药物滥用在内的其他共病。此外，拥有来自 神经心理学特征良好的PWH将促进涉及生物标记物和 神经艾滋病毒背后的免疫因素。CTRSC将通过以下方式实现这些目标：(1)提炼和利用 检查HIV-1疾病参数和一些共病因素的临床队列(SZEP/Pirrone)， (2)运用综合神经心理测评，定性、分型、分型。 HIV-1神经认知损害的相关性(Schultheis/Devlin)，以及(3)病毒学和 免疫学参数(Nonnemacher/Haddad)。CTRSC将与中央行政管理部门对接 和管理核心(CAMC)，并将在目标1和2中与神经艾滋病毒和社区密切合作 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)和 细胞生物学和功能分析核心(CBFAC)帮助培养细胞系并分离和发展原代细胞 细胞群体(目标3)。最后，CTRSC将与职业生涯早期和成熟的调查人员进行互动 在艾滋病毒社区内外利用发展基金开发新的研究问题和拨款 和研究导师核心(DRMC)，并通过在发现、翻译/临床、 或神经艾滋病毒的行为/神经心理学方面。服务将在Drexel进行广泛的内部广告 以及圣殿和外星人。

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.