Clinical Assay to Accurately Profile and Monitor the HIV-1 Reservoir in Chronic-treated Individuals to Guide Treatment Decisions

About This Grant

Project Summary/Abstract Public Health Problem. According to the World Health Organization (WHO), approximately 39 million people are currently living with HIV worldwide. Out of these, about 1.3 million were newly infected in 2022 alone. Moreover, around 630,000 people died from AIDS-related illnesses in the same year. Despite significant advances in therapies and accessibility to care and prevention methods HIV remains a global health challenge. The HIV epidemic has had a severe impact on vulnerable populations, exacerbating existing inequalities. Women and girls are disproportionately affected, accounting for over half of all new HIV infections globally. Despite antiretroviral (ART) initiation upon HIV diagnosis recommended by the 2019 U.S. guidelines, the current chronic-treated and untreated HIV-infected population is >375,000 people in the U.S. alone, and HIV continues to be routinely diagnosed during chronic infection. How Our Product Meets Unmet Needs. Jan Biotech has developed a nonezymatic, chemical amplification and direct detection assay for HIV RNA. The HIVLatentDetect assay provides quick, sensitive, and quantitative measurement of cell-based HIV RNAs in HIV-infected individuals who are fully suppressed under antiretroviral treatment, including for 100% of acute/early HIV-infection treated individuals, for which QVOA, qPCR, ddPCR, IPDA, and single viral copy assays show a ≥25% rate of assay failure or no detection. Jan Biotech’s HIVLD assay provided an unprecedented 0.97 (p-value≤0.0001) predictive value for time to HIV viral rebound after antiretroviral treatment interruption for the acute/early treated cohort in the AIDS Clinical Trials Group (ACTG) A5345. Jan Biotech’s assay would provide a much needed change to HIV standard of care, from viral load testing to detection of reservoir size predictive of, and prior to, plasma viral load changes. HIVLD provides a novel minimal residual disease (MRD) measurement to allow patients and clinicians to make earlier decisions for improving patient care. An MRD assay that captures the replication-competent fraction of chronic HIV reservoirs will allow safer participant involvement in clinical trials investigating new and potential cure or remission treatments. In the long term, HIV MRD testing will facilitate efforts to achieve a functional cure or fully eliminate HIV. Summary of Approach. The proposed work would allow Jan Biotech to expand the assay’s predictive value for time to HIV viral rebound after treatment interruption for the vast chronic-treated HIV-infected population, and to investigate the assay’s value for novel minimal residual disease (MRD) measurements to allow patients and clinicians to make earlier decisions for improving patient care and monitoring response of individual’s chronic HIV reservoir to potential cure treatments. Jan Biotech’s assay of all participating ACTG A5345 assays best captures the functional differences in the HIV reservoir leading to differences in viral rebound time between chronic- and acute/early-treated populations. Collaborators and Unique Resources. Jan Biotech, Inc., with expertise in molecular diagnostic development, will continue to collaborate with Dr. John W. Mellors, University of Pittsburgh School of Public Health; Dr. Michael Keefer, University of Rochester; Dr. Harris Gelbard, Director of the Center for Neurotherapeutics Discovery (CND) and Professor of Neurology, Pediatrics, Neuroscience and Microbiology & Immunology at the University of Rochester Medical Center; and the IVQAC team, led by Dr. Thomas Denny. Specific Aims Specific Aim 1 (Phase I): Develop HIVLD assay to differentiate chronic-treated HIV-1 subpopulations Specific Aim 2 (Phase II): Assay validation using ACTG clinical trial chronic-treated samples Specific Aim 3 (Phase II): Establish large scale clinical relevance for chronic HIV reservoir characterization Specific Aim 4 (Phase II): Software validation and verification for cHIVLD assay analytics Market after Completion. The goal of the proposed work is to develop this very promising technology to serve the vast chronic-HIV population by performing needed testing through HIV treatment interruption and large-scale population studies with well-characterized samples. The chronic-HIVLD assay (cHIVLD) is ideal for routine HIV testing, where it will provide minimal residual disease (MRD) measurements to allow patients and clinicians to make earlier decisions for improving patient care, and for HIV cure trial and research use to monitor the response of individuals’ chronic HIV reservoir to potential cure treatments.