A Novel Test to Measure Latent Virus in HIV-1 Infected Patients

Period of Performance: 06/27/2016 - 05/31/2017

$259K

Phase 1 SBIR

Recipient Firm

Accelevir Diagnostics, LLC
855 N Wolfe Street Rangos Suite B
Baltimore, MD 21205
Principal Investigator

Abstract

Project Summary/Abstract Human immunodeficiency virus type-1 (HIV-1) is a retrovirus that infects CD4+ T cells ofthe immune system. If left untreated, HIV-1 infected individuals will progress to AIDS and mayultimately die as a result. Combination antiretroviral therapy is extremely effective at stoppingthe replication of HIV-1 in infected individuals. Despite the success of this therapy atsuppressing HIV-1 replication to clinically undetectable levels, antiretroviral therapy is notcurative. This is due to the persistence of HIV-1 in a silent, or latent, state within a subset ofCD4+ T cells known as resting memory CD4+ T cells. In this latent state, these infected cells arenot targeted by antiretroviral drugs and cannot be eliminated by the immune system. In HIV-1infected individuals, latently infected CD4+ T cells are found at extremely low frequencies (~1per million resting memory CD4+ T cells). However, this population of latently infected cells isvery stable, demanding that HIV-1 infected individuals remain on antiretroviral therapyindefinitely. Therefore, this population of latently infected CD4+ T cells is the main barrier tocuring 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 thelatent reservoir, we must be able to measure the frequency of latently infected cells using rapidand accurate assays that can be scaled for widespread clinical use. However, such assays arenot currently available. Accelevir Diagnostics, LLC is therefore developing a new molecularassay to accurately measure the size of the latent reservoir by quantifying the number of intact,replication competent proviruses present in CD4+ T cells from HIV-1 infected patients. Broadly,this proposal aims to optimize sample preparation and assay conditions as well as plan andcollect samples for analytical validation studies. The goal of this proposal is to develop anoptimized commercial prototype of our molecular assay for the HIV-1 latent reservoir, withaccompanying standard operating procedures, and set the stage for rapid analytical validationand market entry.