ACCELEVIR DIAGNOSTICS LLC — Department of Health and Human Services SBIR Phase I: NIAID

Description

PROJECT SUMMARY/ABSTRACTHuman immunodeficiency virus type-1 (HIV-1) is a retrovirus that infects CD4+ T cells of the immune system. If left untreated, people living with HIV-1 (PLWH) will progress to AIDS and may ultimately die as a result. Combination antiretroviral therapy (ART) with small-molecule drugs is extremely effective at stopping the replication of HIV-1 in infected individuals but requires daily dosing often with considerable side effects. Importantly, despite the success of this approach 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 long-lived CD4+ T cells at extremely low frequencies. These latently infected cells are not targeted by current small-molecule ART regimens. As a result, PLWH must remain on lifelong antiretroviral therapy.Broadly neutralizing antibodies targeting critical epitopes in HIV-1 Env (HIV-1 bNAbs) are currently being developed as a potential approach to eliminate latent HIV-1 and/or as an alternative to small-molecule ART. HIV-1 bNAbs offer several advantages over traditional small-molecule ART, including the potential for long-acting formulations, reduced side effects, and the potential to eliminate latently infected cells over time. However, a major challenge to the implementation of HIV-1 bNAbs in treatment and cure is pre-existing variation or resistance in the bNAb-targeted epitopes. Scalable clinical tests are needed to determine (1) whether people who will receive HIV-1 bNAbs have pre-existing resistance, and (2) personalize HIV-1 bNAb combinations to each individual. To address this critical unmet need, AccelevirDx is developing the HIV-1 EnvLRS assay as the first scalable sequence-based test to assess HIV-1 bNAb resistance and predict antibody efficacy by in-depth env sequence analysis. Broadly, this proposal aims to (1) analytically qualify AccelevirDx’s novel, proprietary HiFi-dePCR approach for env amplification underlying HIV-1 EnvLRS, (2) determine the reproducibility of the HIV-1 EnvLRS assay of samples from PLWH, and (3) apply the assay to a recently completed ACTG A5340 clinical trial of the HIV-1 bNAb VRC01 in PLWH to assess assay performance and utility.PROJECT NARRATIVEBroadly neutralizing antibodies targeting the HIV Envelope protein (HIV bNAbs) are being developed as a new therapeutic approach to suppress HIV replication and potentially eliminate latent HIV infection in people living with HIV. Scalable clinical tests are needed to determine (1) whether people who will receive HIV bNAbs have pre-existing resistance, and (2) personalize HIV bNAb combinations to each individual. To address this unmet need, Accelevir Diagnostics is developing the HIV-1 EnvLRS assay as the first molecular test to assess HIV bNAb resistance and predict antibody efficacy by in-depth analysis of an HIV-positive person’s HIV envelope gene sequences.