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Towards point of care HIV detection using repurposed glucose meters

使用改造后的血糖仪进行艾滋病毒即时检测

基本信息

批准号：
10899285
负责人：
Suri Saranathan Iyer
金额：
$ 78.85万
依托单位：
UNIVERSITY OF MASSACHUSETTS LOWELL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10899285
关键词：
Acute Address Adopted Anti-Retroviral Agents Antibodies Antigens Antiretroviral resistance Articulation Biological Assay Biomedical Engineering Blood Buffers CASP3 gene Caregivers Chemistry Clinical Clinical Sensitivity Clinical Trials Data Data Aggregation Detection Development Diagnostic tests Disease Engineering Enzyme Precursors Enzymes Equipment Exposure to Feasibility Studies Fingers Goals Grant HIV HIV Protease HIV Seronegativity HIV Seropositivity HIV-1 HIV/AIDS Head Health Personnel Home Human immunodeficiency virus test Incubated Individual Infection Inflammatory Bowel Diseases Influenza Intervention Laboratories Licensing Measures Medical Methods Monitor Neuraminidase Pathogen detection Patients Peptide Hydrolases Peptides Performance Phase Plasma Policy Maker Predisposition Preparation Privacy Process Proteins Qualifying Quality of life Reaction Reporter Reporting Research Reverse Transcriptase Polymerase Chain Reaction Risk Sampling Scientist Sensitivity and Specificity Signal Transduction Silicon Dioxide Technology Testing United States National Institutes of Health Venous Viral Viral Drug Resistance Viral Load result Viremia Virion Virus Whole Blood Work World Health Organization acute infection burden of illness catalyst clinically relevant cytokine design enzyme activity feasibility testing field study glucose monitor high risk improved influenzavirus medical schools milliliter nanomolar novel particle point of care point-of-care diagnostics programs rapid detection self testing seropositive user-friendly virology virus culture volunteer

项目摘要

Project Summary Self-testing of HIV viral load would significantly reduce new infections and provide methods for HIV positive individuals to monitor viral load in the privacy of their own homes. Testing at home followed by analysis of the aggregate data would also assist health care providers, program managers and policy makers to determine the impact of new clinical trials and other interventions. The challenges involved in developing self-testing HIV viral load tests are formidable; for example, the current laboratory tests use milliliters of venous blood extracted in a clinical setting. For self-testing, only microliters of finger stick blood are used, which has low HIV viral copy numbers. To meet these challenges, an interdisciplinary team of scientists with a proven track record has been assembled; the team includes expertise from Chemistry, Biomedical Engineering and Virology. The team has successfully demonstrated the ability to detect influenza virus and measure antiviral susceptibility using repurposed glucose meters in less than 15 minutes. Here, the strategy focuses on detecting HIV protease activity using repurposed glucometers and correlating protease activity to viral load. Since low copy numbers are present in a sample, signal amplification is necessary. In specific aim 1 (R61 phase), a caspase-3 proenzyme bearing HIV protease peptide substrate will be produced. Exposure to HIV protease will result in an active caspase-3 enzyme, which will convert an electrochemically inactive substrate to produce an electrochemically active analyte for detection and qualification with glucometers. In specific aim 2 (R61 phase), mesoporous silica beads capped with anti-HIV protease antibody or peptide substrate will be produced. Inorganic catalysts will be embedded inside the pores of the beads. Exposure to HIV protease will uncap the antibodies or peptide substrate and release the catalysts, which will reach with a substrate to produce an electrochemically active analyte for detection with glucometers. The first two specific aims are designed to be independent of each other to de-risk this high risk, high impact project. Successful execution of specific aims 1 and 2 will lead to specific aim 3 (R33 phase), which would involve testing of the virus from culture and from HIV positive patients. The results from the R33 phase will be compared and contrasted to laboratory based methods including highly accurate PCR methods. At the end of the project period, proof of principle for a novel method that uses repurposed glucose meters to detect HIV during the acute phase and when the viral load increases due to antiviral resistance or discontinuing treatment will be established.

项目总结