Centralized Resource to Accurately Quantify Latent and Expressed HIV Reservoirs

项目概要/摘要 人类免疫缺陷病毒1型（HIV-1）是一种逆转录病毒，感染免疫系统的CD 4 + T细胞， 系统如果不及时治疗，HIV-1感染者将发展为艾滋病，并可能最终死亡。 联合抗逆转录病毒治疗在阻止感染者中HIV-1的复制方面非常有效。 个体尽管这种疗法成功地将HIV-1复制抑制到临床检测不到的水平， 抗逆转录病毒疗法不能治愈疾病。这是由于HIV-1一直处于沉默或潜伏状态 在称为静息记忆CD 4 + T细胞的CD 4 + T细胞亚群中。在这种潜伏状态下，这些被感染的细胞 抗逆转录病毒药物不能靶向它们，免疫系统也不能将其清除。HIV-1感染 在个体中，潜伏感染的CD 4 + T细胞的频率极低（约1/100万静息 记忆性CD 4 + T细胞），大多数在任何给定时间都存在于免疫组织中。这一人口 潜伏感染的细胞非常稳定，要求HIV-1感染者继续接受抗逆转录病毒治疗 以避免病毒血症反弹。因此，这群潜伏感染的CD 4 + T细胞是主要的免疫缺陷病毒。 治疗HIV-1感染的障碍。 开发消除潜伏感染细胞的策略是NIH、NIAID和NIH的主要焦点。 HIV-1研究领域。为了证明针对潜在水库的治疗方法的有效性，我们必须 能够使用快速和准确的测定来测量潜伏感染细胞的频率， 广泛临床应用于外周血和免疫组织。因此， 开发NIAID资源，进行三种创新的分子测定，以准确测量 潜伏库、外周血中存在的残余病毒血症的量以及转录水平。 持久性原病毒的活性。总的来说，这项建议将提供资金，以支持这些机构的业绩， 使用标准操作程序在集中位置为HIV-1治疗研究团体提供检测 用于实验室研究和临床试验。

PROJECT SUMMARY/ABSTRACT Human immunodeficiency virus type-1 (HIV-1) is a retrovirus that infects CD4+ T cells of the immune system. If left untreated, HIV-1 infected individuals will progress to AIDS and may ultimately die as a result. Combination antiretroviral therapy is extremely effective at stopping the replication of HIV-1 in infected individuals. Despite the success of this therapy at suppressing HIV-1 replication to clinically undetectable levels, antiretroviral therapy is not curative. This is due to the persistence of HIV-1 in a silent, or latent, state within a subset of CD4+ T cells known as resting memory CD4+ T cells. In this latent state, these infected cells are not targeted by antiretroviral drugs and cannot be eliminated by the immune system. In HIV-1 infected individuals, latently infected CD4+ T cells are found at extremely low frequencies (~1 per million resting memory CD4+ T cells), with the majority found within immune tissues at any given time. This population of latently infected cells is very stable, demanding that HIV-1 infected individuals remain on antiretroviral therapy indefinitely to avoid rebound of viremia. As such, this population of latently infected CD4+ T cells is the main barrier to curing HIV-1 infection. Developing strategies to eliminate latently infected cells is a major focus of the NIH, NIAID, and the HIV-1 research field. To demonstrate the efficacy of therapeutics targeting the latent reservoir, we must be able to measure the frequency of latently infected cells using rapid and accurate assays that can be scaled for widespread clinical use in both peripheral blood and immune tissues. Accelevir Diagnostics, LLC is therefore developing an NIAID resource to perform three innovative molecular assays to accurately measure the size of the latent reservoir, the amount of residual viremia present in the peripheral blood, and the transcriptional activity of persistent proviruses. Broadly, this proposal will provide funding to support performance of these assays for the HIV-1 cure research community in a centralized location using standard operating procedures for both laboratory research and clinical trials.