Reservoir Dynamics in Patients Treated in Very Early Acute HIV Infection

极早期急性 HIV 感染患者的储库动态

• 批准号: 9203883
• 负责人: Timothy W Schacker
• 金额: $ 65.43万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9203883
• 关键词: Acute; Address; Age; Anatomy; Biological Assay; Biopsy; Cells; Characteristics; Chronic; DNA; Data; Early treatment; Enrollment; Frequencies; Gut associated lymphoid tissue; HIV; HIV Infections; HIV Seropositivity; Helper-Inducer T-Lymphocyte; Human; In Situ; Individual; Infection; Inflammation; Inflammatory; Interruption; Intervention; Knowledge; Lead; Leukapheresis; Location; Lymphoid; Lymphoid Tissue; Maintenance; Methods; Molecular; Nature; Participant; Pathologic; Patients; Procedures; Process; Prospective Studies; Proviruses; Public Health; Publishing; RNA; Red Cross; Research Personnel; Role; Sampling; Staging; Structure; Techniques; Technology; Testing; Thailand; Therapeutic; Time; Tissues; Viral Genome; Viral reservoir; Viremia; Virus; abstracting; antiretroviral therapy; base; cell type; cohort; high risk; immune activation; innovation; insight; lymph nodes; memory CD4 T lymphocyte; new therapeutic target; peripheral blood; seroconversion; sex

Abstract HIV is not cured with current therapeutic strategies. This is because of a large reservoir of cells with HIV proviral DNA that can reactivate and produce new virus. There is a significant gap in our understanding of the dynamic nature of this reservoir, how is it formed, what cellular and anatomic compartments are important, and how it is replenished. We will take advantage of a unique cohort of HIV infected people in Bangkok, Thailand to address these knowledge gaps. These individuals are identified as being HIV+ even before seroconversion because they are at high-risk for HIV infection and are screened frequently. When they are found to be HIV+ they are enrolled into a prospective study where lymphatic tissues are collected on a longitudinal basis. We will apply state of the art molecular and in situ technologies to these serial samples to define the precise size and location of the reservoir and the impact of very early treatment on reservoir size. For comparison we will study age and sex matched individuals started on treatment during chronic infection. The ability to study individuals at each Fiebig Stage of acute infection provides “snapshots” of the reservoir as it is established and will give us insight into the dynamic nature of its formation, maintenance and replenishment. We hypothesize that viral reservoirs become established as early as Fiebig 1, that the cell type supporting the reservoir differs by anatomic location, and that ongoing, persistent immune activation is a significant factor in its replenishment. These data may point to new therapeutic targets to control or eradicate the latent reservoir which is a critical step in the path to a cure of HIV.

摘要 目前的治疗策略无法治愈艾滋病毒。这是因为一个大型水库 这些细胞带有HIV前病毒DNA，可以重新激活并产生新的病毒。有一个 我们对这个水库的动态性质的理解存在重大差距，它是如何形成的？ 形成，什么细胞和解剖隔间是重要的，以及它是如何形成的， 补充。我们将利用一个独特的艾滋病毒感染者群体， 泰国曼谷，以解决这些知识差距。这些人被确认为 即使在血清转换之前也是艾滋病毒阳性，因为他们感染艾滋病毒的风险很高 并经常进行筛查。当他们被发现是艾滋病毒+，他们参加了一个 前瞻性研究，其中纵向收集淋巴组织。我们将 将最先进的分子和原位技术应用于这些系列样品， 水库的精确大小和位置以及早期处理对 水库规模为了比较，我们将研究年龄和性别匹配的个体， 治疗慢性感染。研究每个Fiebig阶段的个体的能力 急性感染的“快照”提供了水库，因为它是建立，并将给予 我们对它的形成、维持和补充的动态性质的洞察力。我们 假设病毒储存库早在Fiebig 1就已经建立， 支持水库的类型因解剖位置而异，持续的，持续的 免疫激活是其补充的重要因素。这些数据可能指向 新的治疗目标，以控制或消除潜在的水库，这是一个关键步骤 在治愈艾滋病毒的道路上。