Accelevir Diagnostics LLC

HIV-1 Envlrs: a Scalable, Sequence-based Assay for In-depth Assessment of HIV-1 Bnab Resistance - 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, 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.