Centralized Resource to Accurately Quantify Latent and Expressed HIV Reservoirs

集中资源准确量化潜在和表达的 HIV 病毒库

基本信息

批准号：
9926700
负责人：
Gregory Michael Laird
金额：
$ 75万
依托单位：
ACCELEVIR DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-13 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9926700
关键词：
Acquired Immunodeficiency Syndrome Address Adoption Anti-Retroviral Agents Biological Assay Blood Volume Blood specimen Businesses CD4 Positive T Lymphocytes Cells Certification Clinical Clinical Trials Communities DNA Data Development Diagnostic Disease remission Ensure Fees Frequencies Funding Genetic Transcription Grant HIV HIV-1 Immune Immune system Individual Industry Infection Infrastructure Integrase Laboratories Laboratory Research Left Location Measurement Measures Molecular Monoclonal Antibody R24 National Institute of Allergy and Infectious Disease Performance Pharmaceutical Preparations Poly A Population Procedures Protocols documentation Proviruses RNA Reagent Recovery Reporting Reproducibility Research Research Personnel Residual state Resources Rest Retroviridae Sampling Services Shock Standardization System Testing Time Tissue Sample Tissues Treatment Efficacy United States National Institutes of Health Viral Viral Load result Viral reservoir Viremia Virus antiretroviral therapy assay development cost cost effective curative treatments design improved innovation memory CD4 T lymphocyte novel therapeutic intervention operation particle peripheral blood programs reagent testing research study side effect success testing services therapeutic target

项目摘要

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.

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，可感染免疫系统的 CD4+ T 细胞系统。如果不及时治疗，HIV-1 感染者将发展为艾滋病，并最终可能因此死亡。联合抗逆转录病毒疗法对于阻止感染者体内 HIV-1 的复制极为有效个人。尽管这种疗法成功地将 HIV-1 复制抑制到临床无法检测到的水平水平，抗逆转录病毒治疗没有疗效。这是由于 HIV-1 持续处于沉默或潜伏状态属于 CD4+ T 细胞的一个子集，称为静息记忆 CD4+ T 细胞。在这种潜伏状态下，这些受感染的细胞不是抗逆转录病毒药物的目标，也不能被免疫系统消除。 HIV-1感染者在个体中，发现潜伏感染的 CD4+ T 细胞的频率极低（约百万分之 1）记忆 CD4+ T 细胞），其中大多数在任何给定时间都存在于免疫组织中。这个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，潜伏感染的 CD4+ T 细胞群是主要的治愈 HIV-1 感染的障碍。制定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库的治疗方法的功效，我们必须能够使用快速、准确的测定法来测量潜伏感染细胞的频率，这些测定法可以扩展临床广泛应用于外周血和免疫组织。因此，Accelevi Diagnostics, LLC 是开发 NIAID 资源来执行三种创新的分子测定，以准确测量潜伏病毒库、外周血中残留病毒血症的量以及转录病毒持久性原病毒的活性。总体而言，该提案将为支持这些项目的绩效提供资金使用标准操作程序在集中地点为 HIV-1 治愈研究界进行检测用于实验室研究和临床试验。