Comprehensive NeuroHIV Center

摘要 目前对HIV-1感染的治疗已经改变了疾病的面貌，改变了曾经急性致命的 从疾病到慢性病。因此，出现了许多其他需要密切关注的问题，包括 与病毒基因组的存在相关的共病，以及ART对 一些组织和细胞，包括大脑，它们影响神经细胞的动态平衡，从而有助于 艾滋病毒携带者(PWH)中出现的神经认知和行为障碍。其他值得关注的领域 与威斯康星社区神经性艾滋病毒差异的社会和结构决定因素有关。现在，它已经变成了 越来越清楚地认识到，必须通过采用复杂、创新、下一步 旨在永久消除威尔斯亲王医院和威尔斯亲王医院艾滋病毒-1的产生方法和技术 在细胞和分子水平上保护未感染的个人免受艾滋病毒-1感染。重要的是，一个类似的 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40多年的临床 艾滋病毒-1感染带来的挑战。通过整合我们在天普和德雷克塞尔团队的资源和专业知识， 我们已经开发了一个综合神经艾滋病毒中心(CNHC)设施，为来自 大费城地区和更远的地方，发起和研究与神经科学相关的当前问题 将艾滋病毒-1从社区推广到实验室和临床，重点放在神经精神/行为(一个新领域 重点)，关于艾滋病毒-1感染的神经科学的持续研究，以及治疗策略的发展 在分子和细胞水平上通过使用基因从宿主中消除HIV-1前病毒DNA 采用CRISPR等基于基因编辑的技术。我们认为，这一独特而史无前例的 战略将在改善威尔斯亲王医院社区目前与艾滋病毒-1感染相关的挑战方面具有双重效益 并为开发缓解/消除病毒感染的新方法提供了新的机会 由一个高度合作和互补的科学家小组。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 非西班牙裔或西班牙裔血统，以深度测序和详细的免疫表型为特征 在临床和翻译研究支持核心(CTRSC)中描述，与NeuroHIV密切合作 社区伙伴关系和差异核心(NHCPDC)，并利用 病毒基因编辑和生物信息学核心(VGEBC)，以及由细胞生物学和 功能分析核心(CBFAC)，以及发展所提供的金融和智力机会 研究和指导核心(DRMC)。所有这些都是由中央银行在业务上进行优化和协调的 行政和管理核心(CAMC)，以最大限度地实现我们的成就。

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.