Monitoring HIV Antiretroviral Therapy via Aptamer-Based Measurements in Preclinical Animal Models, in Human Plasma

Abstract

Monitoring the concentration of antiretroviral drugs is critical to ensuring patient adherence to HIV treatment and prevention regimens, which is crucial for drug efficacy. These tools may also be useful for screening samples at blood donation centers to avert potential new infections. The current benchmark method to support antiretroviral drug monitoring, liquid chromatography coupled to mass spectrometry (LC-MS), requires centralized facilities with costly instrumentation, and has blood-to-result turnaround times of days to weeks, making it impractical for effective drug monitoring. Seeking to overcome this issue, an aptamer is developed for the antiretroviral drug emtricitabine, which is present in most antiretroviral combination therapies in the market and used for both infection management and prevention. The aptamer has clinically relevant sensitivity in biofluids and is highly selective relative to close analogs such as cytosine, cytidine, fluorocytidine, and lamivudine (a.k.a. 3TC). Using this aptamer, two analytical assays are developed, one for continuous, in-vivo emtricitabine monitoring in rodent research models, and one for rapid and high-throughput screening of emtricitabine levels in human plasma. Through blinded analytical validation, this clinical assay achieved an 86.9% positive and 100% negative correlation, with an overall agreement rate of 95% relative to the benchmark LC-MS method.