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

项目2.晚期治疗摘要：血液和组织储存库 大多数人体研究的特点是循环宿主和一些非血液HIV宿主使用有限的 来自其他健康的艾滋病毒感染者的生物样本，如生殖器切片、肠道活检和 脑脊液，或尸检标本，鲜有尸检特征。因此，我们的理解是 艾滋病毒如何在人体内填充组织，以及这些组织是如何相互关联的-- 仍然是有限的。我们提议的在反弹期间揭示水库(R3)计划将采取以下步骤 通过了解艾滋病毒如何持续存在并在体内蓄积来寻找治愈艾滋病毒的方法。 具体来说，晚期治疗研究项目(RP)将最大限度地利用从 “最后一份礼物”是一群感染艾滋病毒的绝症患者。这些利他的个人将提供：(I)详细的 死亡前的临床、风险和社会人口学信息；(2)在死亡期间每周采血 在自愿停止抗逆转录病毒治疗前后的活着，以及(Iii)他们死后的全身。这群人将允许 美国将在抗逆转录病毒疗法停止前和反弹病毒血症期间确定血液中艾滋病毒种群的特征，以及 在死后遍及全身。为了补充早期治疗RP中提出的研究，该RP将 确定： 目标1：在抗逆转录病毒治疗期间测量的病毒学和免疫学参数预测病毒反弹的动态 艺术停止时的动态(时间、大小、斜率)； 目的2：抗逆转录病毒治疗后HIV变异株在CD4+T细胞亚群和不同解剖组织中的动态变化 中断。 目的3：确定抗逆转录病毒治疗期间和术后与艾滋病毒持久性有关的免疫学机制 中断。 通过调查在慢性感染期间开始抗逆转录病毒治疗并因此携带较大艾滋病毒的艾滋病毒感染者 艾滋病病毒对机体的免疫损伤较多，后期治疗将配合RP早期治疗 它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，因此有较小的 艾滋病毒蓄水池和更完整的免疫系统。这个RP还将创造关于HIV如何 存在于循环中的CD4+T细胞和解剖组织中，这些数据将与 从早期处理RP的数据看，新的分析方法与RP的定量方法相比更加充分 了解人体内艾滋病毒的动态变化。

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.