Monitoring SIV reservoirs with whole body immunoPET

随着新的抗逆转录病毒疗法的出现，潜在消除艾滋病毒/艾滋病的前景将变得更加光明。 从受感染的患者身上获得艾滋病毒可能成为一个可以实现的目标。然而，这一目标需要 新的工具，比现有的更敏感，以监测这种进展， 治疗，不仅在血液中，而且在器官中，也窝藏这样的水库和网站的残留 体内病毒复制。此外，在急性胰腺炎期间， 相对于传播途径和疾病进展的感染可能会打开新的 化学治疗或免疫屏障的指导，以包含新的病毒感染福耶斯， 广泛传播的感染与播种的病毒水库。这么早就利用 病毒动力学并解释了这种动力学存在的自然个体差异， 有必要了解粘膜感染后HIV感染的传播模式 传播是全球感染的主要传播方式。然而，工具 目前可用于监测这种病毒过程的方法是间接的或相对侵入性的， 显然对人类诊所来说不切实际。即使使用非人类灵长类动物模型， 艾滋病，了解病毒的动态在真实的时间是具有挑战性的和昂贵的，如果 一个人选择进行一系列的牺牲，更不用说充满了高度的可变性 个体之间的关系。在这个项目中，我们建议优化我们建立的免疫正电子 发射断层扫描（PET）与同步X射线计算机断层扫描（CT），以确定 猴免疫缺陷病毒在体内复制位点的实时全身图谱， SIV在体内的全身复制位点，并确定病毒动力学和残留位点。 抗逆转录病毒治疗期间的病毒复制。因此，我们建议确定解剖SIV 通过IV、直肠和阴道途径感染后的病毒动力学，以确定 体内病毒复制的连续主要位点，这将通过靶组织确认 收藏.接下来，我们将比较2种减少病毒库的联合ART疗法， 记录体内复制的残留福耶斯，并确定哪些这样的储库可能 在体内ART中断后，我们认为，这些研究将 为设计人类艾滋病毒感染的艾滋病毒根除战略提供关键信息。

With the advent of novel anti-retroviral therapies, the prospect of potentially eliminating HIV from infected patients may become an achievable goal. However, such goal will require new tools with greater sensitivity than currently available to monitor the progress of such therapy, not only in blood but also in organs that do harbor such reservoirs and sites of residual viral replication in vivo. In addition, identifying early seeding of viral reservoirs during acute infection relative to the route of transmission and disease progression may open novel directions for chemotherapeutic or immune barriers to contain the new virus infection foyers and generalized dissemination of the infection with seeding of viral reservoirs. To harness such early viral dynamics and account for the natural individual variation that exists for such dynamics, there is a need to understand the dissemination patterns of HIV infection following mucosal transmission, the primary transmission mode of infection worldwide. However, the tools currently available to monitor such viral processes are either indirect or relatively invasive and clearly impractical for the human clinic. Even when one uses the nonhuman primate model of AIDS, understanding the viral dynamics in real time is challenging and prohibitively expensive if one chooses to perform serial sacrifices, not to mention fraught by a high degree of variability between individuals. In this project, we propose to optimize our established immuno-positron emission tomography (PET) with simultaneous X-ray computed tomography (CT), to determine real-time whole body maps of simian immunodeficiency virus replication sites in vivo to chart out the total body replication sites of SIV in vivo and determine viral dynamics and sites of residual viral replication during antiretroviral therapy. Thus we propose to determine the anatomic SIV viral dynamics following infection via the IV, rectal and vaginal route to determine the consecutive major sites of viral replication in vivo, which will be confirmed via targeted tissue collections. Next we will compare 2 combination ART therapies for reducing viral reservoirs and document residual foyers of replication in vivo as well as determine which such reservoirs might be fueling the viral resurgence after interruption of ART in vivo. We submit that these studies will provide critical information for the design of HIV eradication strategies in human HIV infection.