Centralized Resource to Accurately Quantify Latent and Expressed HIV Reservoirs

项目摘要/摘要 人类免疫缺陷病毒1型(HIV-1)是一种逆转录病毒，感染免疫的CD4T细胞 系统。如果不进行治疗，HIV-1感染者将发展为艾滋病，并可能最终死亡。 联合抗逆转录病毒疗法在阻止HIV-1在感染者体内复制方面极其有效 个人。尽管这种疗法成功地将HIV-1复制抑制到临床无法检测到 水平，抗逆转录病毒治疗是不能治愈的。这是由于HIV-1持续处于沉默或潜伏状态 在被称为静息记忆的CD4T细胞的一个子集内。在这种潜伏状态下，这些被感染的细胞 不是抗逆转录病毒药物的靶点，也不能被免疫系统消除。在感染了HIV-1的人中 在个体中，潜伏感染的CD4T细胞被发现的频率极低(每百万人中有一人处于静息状态 记忆CD4T细胞)，在任何给定的时间，大多数存在于免疫组织中。这一人口 潜伏感染细胞非常稳定，要求HIV-1感染者继续接受抗逆转录病毒治疗 无限期避免病毒血症反弹。因此，这种潜伏感染的CD4T细胞是主要的 治愈HIV-1感染的障碍。 开发消除潜伏感染细胞的策略是NIH、NIAID和 HIV-1研究领域。为了证明针对潜在储蓄者的疗法的有效性，我们必须 能够使用快速而准确的分析方法测量潜伏感染细胞的频率，该方法可根据需要进行调整 在临床上广泛应用于外周血和免疫组织。因此，Acelevir诊断有限责任公司 开发NIAID资源，执行三种创新的分子分析，以准确测量 潜伏库，外周血中残留病毒血症的量，以及转录 持续性前病毒的活动。总的来说，这项提案将提供资金，以支持这些项目的业绩 使用标准操作程序在集中地点为HIV-1治愈研究社区进行分析 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.