Studies in humans to delineate the basis for viral persistence

无论有效的抗逆转录病毒疗法的发展如何，没有一个艾滋病毒感染者被治愈 (艺术)。然而，感染的稳定缓解或治愈是艾滋病毒治疗的最终目标。困难所在 终身治疗的重要性使我们必须了解根除艾滋病毒感染的障碍，并 试着克服它们。除了改进的抗病毒药物外，诱导潜伏的艾滋病毒表达的药物 不加强从头感染是必要的。 首先，最近的研究表明，HIV感染可能会持续存在于一系列CD4记忆细胞群体中， 可能与ART抑制病毒血症所达到的疾病阶段有关。因此，我们必须 具体表征记忆细胞亚群中持续感染的频率(例如，天真的， 中心、过渡性、效应者)，并调查对以下因素的潜在反应差异 干扰潜伏期。如果未来的抗潜伏期疗法要在所有人中都有效，这将是重要的信息 记忆细胞亚群，以及在所有患者群体中。 第二，整个Deianey合作实验室的研究人员将开发新的方法和分子来 在各种模型系统中干扰和耗尽潜在的艾滋病毒感染，并将发现新的 建立或维持潜在艾滋病毒感染的机制。然而，要将这些进展推向临床 翻译，这个项目将通过对终极模型的研究来促进合作实验室的进步 系统--从接受抗逆转录病毒治疗的无氧血症患者体内获得的静息的CD4+T细胞。 特异性目标I：静息性CD4+T细胞在中枢和移行区感染的频率和效应器 在急性或慢性艾滋病毒感染期间接受治疗的患者的记忆细胞会有所不同。 具体目标11：将发现单独或与其他试剂协同作用的新分子 (例如，SAHA)扰乱接受ART治疗的HIV感染的无氧血症患者的静息CD4+T细胞的潜伏期。 特定目标III：靶向限制HIV+患者静息CD4+T细胞的表达将导致 病毒式增长。

No one with HIV infection has been cured, regardless of the development of effective antiretroviral therapy (ART). Nevertheless, stable remission or cure of infection is the ultimate goal of HIV therapy. The difficulties of lifelong therapy make it imperative to understand the obstacles to eradication of HIV infection, and to attempt to overcome them. In addition to improved antivirals, agents that induce expression of latent HIV but do not enhance de novo infection are needed. First, recent studies suggest that HIV infection may persist in a spectrum of CD4 memory cell populations, perhaps related to the stage of disease reached when viremia is suppressed by ART. Therefore, we must specifically characterize the frequency of persistent infection in memory cell subpopulations (eg. naive, central, transitional, effector), and investigate the potential differences in responsiveness to agents that perturb latency. This will be important information if future anti-latency therapies are to be effective in all memory cell subsets, and in all patient populations. Second, across the Deianey Collaboratory investigators will develop new approaches and molecules to disrupt and deplete latent HIV infection across a wide variety of model systems, and will discover new mechanisms that establish or maintain latent HIV infection. However to move these advances toward clinical translation, this project will contribute to the advances ofthe Collaboratory via studies in the ultimate model system - - resting CD4+ T cells obtained from aviremic, ART-treated patients. Specific Aim I: The frequency of resting CD4+ T cell infection in central and transitional, and effector memory cell will differ in patients treated during acute or chronic HiV infection. Specific Aim 11: Novel molecules will be discovered that alone or in synergy with other reagents (eg. SAHA) disrupt latency in the resting CD4+ T cells of HIV-infected aviremic,ART-treated patients. Specific Aim III: Targeting restrictions to expression in the resting CD4+ T cells of HIV+ patients will induce viral outgrowth.