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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：
10596211
负责人：
Gregory Michael Laird
金额：
$ 147.63万
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/10596211
关键词：
Acceleration Acquired Immunodeficiency Syndrome Address Adoption Anti-Retroviral Agents Binding Biological Assay Blood Volume Blood specimen Businesses CD4 Positive T Lymphocytes CLIA certified Cells Clinical Clinical Trials Communities DNA Data Dedications Development Diagnostic Disease remission Fees Frequencies Funding Genetic Transcription Grant HIV HIV-1 Immune Immune system Individual Industry Infection Infrastructure Integrase Laboratories Laboratory Research Left Life Location Measurement Measures Molecular National Institute of Allergy and Infectious Disease Performance Pharmaceutical Preparations Poly A Polyadenylation Population Procedures Protocols documentation Proviruses Qualifying R24 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 immune clearance 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.

项目总结/文摘