Reservoir Dynamics in Patients Treated in Very Early Acute HIV Infection

摘要 目前的治疗策略并不能治愈艾滋病毒。这是因为有一个大型水库 携带艾滋病毒前病毒DNA的细胞可以重新激活并产生新病毒。有一个 在我们对这个水库的动态性质的理解上有很大的差距，它是如何 形成的，什么细胞和解剖间隔是重要的，以及它是如何形成的 补充好了。我们将利用一群独特的艾滋病毒感染者 泰国曼谷，以解决这些知识差距。这些人被确认为 甚至在血清转换之前就是HIV+，因为他们感染HIV的风险很高 并经常接受筛查。当他们被发现是HIV+时，他们就会参加 纵向收集淋巴组织的前瞻性研究。我们会 将最先进的分子和原位技术应用于这些系列样品，以确定 水库的准确大小和位置以及早期治疗对 水库大小。为了进行比较，我们将研究年龄和性别匹配的个体 慢性感染期间的治疗。在每个阶段研究个体的能力 提供了水库建立时的“快照”，并将给出 美国对其形成、维护和补充的动态性质的洞察。我们 假设病毒储存库早在FieBig 1就建立了，那么细胞 支持储集层的类型因解剖位置不同而不同，并且持续的、持久的 免疫激活是其补充的一个重要因素。这些数据可能指向 控制或根除潜伏性油藏的新治疗目标是关键的一步 在治愈艾滋病毒的道路上。

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.