ABSTRACT Adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are critical to the success of HIV treatment and therapeutic prevention. No accurate, objective point-of-care test is available to monitor adherence to either ART or PrEP. The inability to accurately identify poorly adherent patients will lead to more HIV infections (from failed PrEP and non-suppressive ART), more drug-resistant virus (selected by failing ART), and unnecessary switching to costly second- or third-line ART (when first-line regimens with virologic efficacy but non-adherence are stopped inappropriately). To address this critical knowledge gap, we have developed a novel point-of-care test to detect the presence of tenofovir—the most common drug in both ART and PrEP treatments worldwide—in fingerprick blood or urine as an objective measure of ART and PrEP adherence. The objective of our application is to conduct essential next-step work to advance this point-of-care test: we will assess our novel point-of-care assay in whole blood and urine specimens within a controlled pharmacokinetic study of healthy volunteers maintaining controlled drug adherence and conduct a pilot validation study of our novel point-of-care assay on real-world clinical samples from an existing biorepository. Our central hypothesis is that the pharmacokinetics of tenofovir in blood and urine will support point-of-care tenofovir detection as an objective measure of adherence, and that our point-of-care tenofovir assay will have the ability to discriminate different drug adherence levels. We will test our central hypotheses by pursuing the following two specific aims: (1) To assess our novel point-of-care tenofovir (TFV) assay in whole blood and urine specimens within a controlled pharmacokinetic study of HIV-negative adults receiving tenofovir disoproxil fumarate (TDF) with low, moderate, and perfect adherence; and (2) To validate our novel point-of-care tenofovir (TFV) assay on blood and urine specimens using an existing biorepository from a real-world clinical HIV prevention study. This work is innovative because it develops an entirely new category of rapid diagnostic testing for monitoring ART and PrEP adherence at the clinical point of care. Our rapid assay will help clinicians identify patients in need of more adherence counseling, which when implemented will prevent HIV acquisition, emergence of drug- resistant virus, and unnecessary ART regimen switching—measures that will improve national HIV programs and help preserve the global supply of an effective HIV medication.

NARRATIVE Adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are critical to the success of HIV treatment and therapeutic prevention. No accurate, objective point-of-care test is available to monitor adherence to either ART or PrEP, which leads to more HIV infections, more drug-resistant virus, and thousands of people in resource-limited settings being inappropriately switched to costly second- or third-line ART. We have developed a novel point-of-care test to detect the presence of tenofovir—the most common drug in both ART and PrEP treatments worldwide—and we plan to establish the pharmacokinetics of tenofovir in fingerprick whole blood and urine and performance with our assay, and to perform a pilot validation study of our novel point-of- care assay using real-world clinical samples.