Highly specific HIV mRNA detection method with global subtype coverage to monitor latency reversal in patients

Project Summary Abstract Human immunodeficiency virus type HIV is a retrovirus that infects CD T cells of the immune system If left untreated HIV 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 in infected individuals Despite the success of this therapy at suppressing HIV replication to clinically undetectable levels antiretroviral therapy is not curative This is due to the persistence of HIV in a silent or latent state within a subset of CD T cells known as resting memory CD 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 infected individuals latently infected CD T cells are found at extremely low frequencies per million resting memory CD T cells However this population of latently infected cells is very stable demanding that HIV infected individuals remain on antiretroviral therapy indefinitely Therefore this population of latently infected CD T cells is the main barrier to curing HIV infection Developing strategies to eliminate latently infected cells is a major focus of the NIH NIAID and the HIV research field One primary strategy involves the reactivation of latent infected cells driving their elimination We need sensitive validated molecular assays to monitor this reactivation of latently infected cells in patients receiving such therapeutics The most direct way to quantify reactivation is to measure the induction of intracellular HIV mRNA yet current methods suffer from critical shortcomings Accelevir Diagnostics LLC is developing a new quantitative assay to measure intracellular HIV mRNA in infected patients Importantly this assay will cover globally distributed HIV subtypes Broadly this proposal aims to optimize the assay perform key assay validation studies and define baseline intracellular HIV mRNA values for ART suppressed individuals The goal of this proposal is to develop an optimized commercial prototype with accompanying standard operating procedures and set the stage for rapid analytical validation and market entry !Project Narrative For HIV infected individuals on suppressive antiretroviral therapy latent HIV infection of resting memory CD T cells is the major barrier to a cure Reactivation of these latently infected cells by has been proposed as a strategy to cure infected individuals This proposal details the development and optimization of a new molecular assay to measure the reactivation of infected cells in patients by Accelevir Diagnostics for use in monitoring the efficacy of HIV cure therapies