Description | Towards a rapid and accessible test for measuring antiviral drug levels to improve Human Immunodeficiency Virus (HIV) treatment and prevention Ayokunle Olanrewaju, Acting Assistant Professor, UW Mechanical Engineering Tuesday, Oct 6, 2020 @ 3:30pm Recording: www.youtube.com… Abstract: Poor adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) can lead to human immunodeficiency virus (HIV) acquisition and emergence of drug-resistant infections, respectively. Measurement of antiviral drug levels provides objective adherence information that may help prevent adverse health outcomes. HIV drug level measurement is typically carried out using liquid chromatography/mass spectrometry (LC/MS) which is centralized, heavily instrumented, and expensive and is thus unsuitable and unavailable for routine use in clinical settings. We developed the REverSe TRanscrIptase Chain Termination (RESTRICT) assay as a rapid and accessible measurement of HIV drug levels. The assay uses designer single-stranded DNA templates and intercalating fluorescent dyes to measure complementary DNA (cDNA) formation by HIV reverse transcriptase enzyme in the presence of nucleotide reverse transcriptase inhibitor drugs. Guided by a probabilistic model, we optimized the RESTRICT assay to detect clinically relevant concentrations of tenofovir diphosphate (TFV-DP), a metabolite that indicates long-term ART and PrEP drug levels. We developed simple and user-friendly sample preparation strategies to detect intracellular TFV-DP in patient whole blood. We completed a pilot evaluation using real patient samples and identified individuals with TFV-DP concentrations above the threshold for adequate adherence (≥ 4 doses/week) with good correlation with LC/MS measurements. The RESTRICT assay is a fast and accessible test that could be useful for patients and clinicians to improve HIV/AIDS treatment and prevention outcomes.Bio: Dr. Ayokunle Olanrewaju is an Acting Assistant Professor in the Mechanical Engineering Department at UW. He received undergraduate and master’s degrees in Electrical Engineering at the University of Alberta in Canada and completed a Ph.D. in Biological and Biomedical Engineering at McGill University with his dissertation focused on 3D-printed microfluidic circuits for self-powered and self-regulated bioassays. Afterwards, he worked as an industrial postdoctoral fellow with Sensoreal – a startup that aimed to commercialize self-powered microchips for rapid diagnosis of urinary tract infections in infants. He completed a postdoctoral fellowship in Professor Jonathan Posner’s group at UW. His current research at UW is focused on developing rapid and user-friendly tests for monitoring medication drug levels in near-patient settings to improve disease treatment and prevention outcomes in global health settings. See more about his research accomplishments and interests here. * The seminar is part of the ME Graduate Seminar Series (ME 520) |
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