Activity-Based Assays for Monitoring Treatment and Prevention of Infectious Diseases

For many infectious and chronic diseases, effective medications already exist, and prevention or treatment succeeds or fails on whether those drugs are dosed and taken correctly. Concentrations that are too low lead to new infection or treatment failure, and concentrations that are too high cause adverse reactions. Current methods for measuring drug concentrations are expensive, labor-intensive, and slow, which puts them out of reach for most people who would benefit from them. Rapid and inexpensive tests would make monitoring and dose individualization far more widely available, from centralized laboratories to the bedside and the home, and particularly in resource-limited settings.

Our lab develops tests that measure drug concentrations using the drugs’ own biochemical activity rather than by detecting the drug molecules themselves. We have built user-friendly tests that measure the active intracellular forms of several human immunodeficiency virus (HIV) medications, with excellent concordance with gold-standard mass spectrometry. We extended this approach to therapeutic drug monitoring of cytomegalovirus (CMV) medications, measuring ganciclovir triphosphate in infants with congenital CMV, where dosing must avoid both underexposure and toxicity. The same need applies to transplant recipients and other immunocompromised populations. Most recently, we inverted our assay principle: by measuring the activity of reverse transcriptase derived from patient samples, rather than recombinant enzyme, we can measure HIV viral load and detect phenotypic drug resistance in the same rapid and user-friendly format.

Our current focus is on optimizing, validating, and delivering these tests to populations in need both locally and globally, building a unified toolkit for monitoring drug exposure, viral suppression, and drug resistance at the point of need.

Speaker: Ayokunle Olanrewaju, PhD, University of Washington