Comprehensive NeuroHIV Center

摘要 目前对 HIV-1 感染的治疗已经改变了这种疾病的面貌，将曾经急性致命的病毒转变为病毒。 疾病转为慢性疾病。因此，许多其他问题也浮出水面，需要密切关注，包括 与病毒基因组存在相关的合并症，以及 ART 对患者的潜在副作用 包括大脑在内的多种组织和细胞会影响神经元细胞的稳态，从而有助于 HIV 感染者 (PWH) 中出现的神经认知和行为障碍。其他值得关注的领域 与 PWH 社区中 NeuroHIV 差异的社会和结构决定因素有关。现在，已经成为了 越来越清楚的是，必须通过采用先进的、创新的、下一代的技术来解决问题 旨在永久消除艾滋病毒感染者和艾滋病毒感染者中 HIV-1 的生成方法和技术 在细胞和分子水平上保护未感染者免受 HIV-1 感染。重要的是，平行 改善艾滋病毒社区神经认知/心理障碍的方法以及使用 必须实施消除/保护的分子策略，以结束四十多年的临床 HIV-1 感染带来的挑战。通过结合坦普尔和德雷塞尔团队的资源和专业知识， 我们建立了综合性 NeuroHIV 中心 (CNHC) 设施，为来自各个领域的科学家提供服务 大费城地区及其他地区发起并调查当前与神经科学相关的问题 HIV-1从社区到实验室和诊所的研究，重点是神经精神/行为（一个新领域 重点），继续研究 HIV-1 感染的神经科学以及治疗策略的制定 通过使用基因技术从宿主中消除 HIV-1 前病毒 DNA，在分子和细胞水平上 方法，例如基于 CRISPR 基因编辑的技术。我们建议，这种独特且前所未有的 该战略对于改善艾滋病毒感染者社区当前与 HIV-1 感染相关的挑战具有双重好处 并为开发减轻/消除病毒感染的新方法提供新的机会 由高度协作和互补的科学家小组完成。我们的目标仍然是提供神经艾滋病毒研究 基础设施和支持 利用和扩展 CNHC 丰富的临床神经心理学数据 PWH 的纵向队列，主要包括黑人/非裔美国人和白人参与者，他们认为 通过深度测序和详细的免疫表型分析充分表征非西班牙裔或西班牙裔血统： 与 NeuroHIV 密切合作，在临床和转化研究支持核心 (CTRSC) 中进行了描述 社区伙伴关系和差异核心 (NHCPDC) 并利用以下机构提供的专家服务 病毒基因编辑和生物信息学核心 (VGEBC)，以及细胞生物学和生物信息学中心提供的资源 功能分析核心（CBFAC），以及发展提供的财务和智力机会 研究和指导核心（DRMC）。所有这些都是由中央在操作上优化和精心策划的 行政和管理核心 (CAMC) 最大限度地提高我们的成就。

SUMMARY Current treatment of HIV-1 infection has changed the face of the disease by converting a once acute deadly disease to a chronic illness. As such, many other issues have surfaced that require close attention including comorbidities associated with the presence of the viral genome, as well as the potential side effects of ART on several tissues and cells including brain that impact on the homeostasis of neuronal cells thus contributing to neurocognitive and behavioral disorders seen among people living with HIV (PWH). Other areas of concern relate to social and structural determinants of NeuroHIV disparities in the PWH community. Now, it has become increasingly clear that the landscape must move toward a cure by employing sophisticated, innovative, next generation approaches and technologies that are aimed at the permanent elimination of HIV-1 in PWH and protect uninfected individuals from HIV-1 infection at the cellular and molecular levels. Importantly, a parallel approach to improve neurocognitive/psychological disorders in the HIV community as well as the use of molecular strategies for elimination/protection must be implemented to end more than four decades of clinical challenges caused by HIV-1 infection. By combining resources and expertise of our teams at Temple and Drexel, we have developed a Comprehensive NeuroHIV Center (CNHC) facility to provide services to scientists from the greater Philadelphia area and beyond to initiate and investigate the current issues associated with neuroscience of HIV-1 from community to laboratory and clinic with an emphasis on neuropsychiatric/behavioral (a new area of emphasis), continued studies on the neuroscience of HIV-1 infection, and the development of cure strategies at the molecular and cellular levels by the elimination of HIV-1 proviral DNA from the host using a genetic approach such as CRISPR gene editing-based technologies. We propose that this unique and unprecedented strategy will have dual benefit in improving current challenges associated with HIV-1 infection in PWH community and offer new opportunities for the development of a novel approach for mitigation/elimination of viral infection by a highly collaborative and complementary group of scientists. Our goals remain to provide neuroHIV research infrastructure and support utilizing and expanding the CNHC's rich clinical neuropsychological data from a longitudinal cohort of PWH, including primarily Black/African-American and White participants that identify as non-Hispanic or Hispanic origin well-characterized by deep sequencing and detailed immunophenotyping as described in the Clinical and Translational Research Support Core (CTRSC), working closely with NeuroHIV Community Partnership and Disparities Core (NHCPDC) and taking advantage of the expert services offered by Viral Gene Editing and Bioinformatics Core (VGEBC), together with resources offered by the Cell Biology and Functional Analysis Core (CBFAC), and the financial and intellectual opportunities offered by the Developmental Research and Mentorship Core (DRMC). All of which are operationally optimized and orchestrated by the Central Administrative and Management Core (CAMC) to maximize our achievements.