Late Treatment Research Project (RP): Blood and Tissues Reservoirs

项目2.后期治疗摘要：血液和组织储库 大多数人类研究都使用有限的HIV抗体来表征循环水库和一些非血液HIV水库。 来自其他健康的HIV感染者的生物样本，如生殖器切片，肠道活检， 脑脊液，或尸检标本，几乎没有死前特征。因此，我们的理解 艾滋病病毒如何在全身组织中繁殖，以及这些种群如何相互关联- 仍然有限。我们提议的回弹期间揭示储层（R3）计划将采取以下步骤： 通过了解艾滋病毒如何在体内持续存在并在整个身体的水库中繁殖来找到艾滋病毒的治疗方法。 具体来说，后期治疗研究项目（RP）将最大限度地利用从一个国家收集的数据和样本， 感染艾滋病毒的绝症患者的“最后礼物”队列。这些利他主义者将提供：（一）详细的 （二）死亡前的临床、风险和社会人口统计信息;（三）死亡后每周采集一次血液; 在自愿停止抗逆转录病毒疗法之前和之后，以及（iii）他们死亡后的整个身体。这批人将允许 我们在ART停止前和病毒血症反弹期间描述血液中的HIV人群， 在死后的身体里。为了补充早期治疗RP中提出的研究，本RP将 确定： 目的1：ART期间测量的病毒学和免疫学量可预测病毒反弹的动力学 ART停止时的动态（定时、大小、斜率）; 目的2：ART后HIV变体在CD 4 + T细胞亚群和各种解剖组织中的动态 中断. 目的3：确定ART期间和ART后与HIV持续存在相关的免疫机制 中断. 通过调查在慢性感染期间开始ART的HIV感染者， 水库和更多的免疫损伤，从艾滋病毒，后期治疗RP将补充早期治疗 RP将调查在急性和早期感染期间开始抗逆转录病毒治疗的人， 艾滋病病毒库和更完整的免疫系统。该RP还将创造关于艾滋病毒如何 存在于循环CD 4 + T细胞和解剖组织中，这些数据将结合 数据从早期治疗RP通过新的分析方法与定量方法RP更充分 了解艾滋病毒在全身的动态。

PROJECT 2. LATE TREATMENT ABSTRACT: Blood and Tissues Reservoirs Most human studies have characterized circulating reservoirs and some non-blood HIV reservoirs using limited biological samples from otherwise healthy HIV-infected individuals, like genital sections, gut biopsies and cerebrospinal fluid, or autopsy specimens with little pre-mortem characterization. Therefore, our understanding of how HIV populates tissues throughout the body and how these populations are associated with each other- remains limited. Our proposed Revealing Reservoirs during Rebound (R3) program will take the next steps in finding a cure for HIV by understanding how HIV persists in and populates reservoirs throughout the body. Specifically, the Late Treatment Research Project (RP) will maximize data and samples collected from a `Last Gift' cohort of HIV-infected terminally-ill individuals. These altruistic individuals will provide: (i) detailed clinical, risk and socio-demographic information before their death; (ii) weekly blood collections while they are alive, before and after voluntarily stopping ART and, (iii) their entire bodies after they die. This cohort will allow us to characterize the HIV populations in blood before ART is stopped and during rebound viremia, and throughout the body after death. To complement studies proposed in the Early Treatment RP, this RP will determine: Aim 1: Virologic and immunologic quantities measured during ART that predict dynamics of viral rebound dynamics when ART is stopped (timing, size, slope); Aim 2: Dynamics of HIV variants populating CD4+ T cell subsets and in various anatomic tissues after ART interruption. Aim 3: Determine immunologic mechanisms associated with HIV persistence during ART and after ART interruption. By investigating HIV-infected individuals who started ART during chronic infection and thus have larger HIV reservoirs and more immune damage from HIV, the Late Treatment RP will complement the Early Treatment RP, which will investigate persons who started ART during acute and early infection, and thus have smaller HIV reservoirs and more intact immune systems. This RP will also create new knowledge about how HIV resides in circulating CD4+ T cells and in anatomic tissues, and these data will be analyzed in conjunction with data from the Early Treatment RP vianew analytical methods with the Quantitative Methods RP to more fully understand HIV dynamics throughout the body.