Point-of-care Urine Monitoring of Adherence (PUMA): Testing a Real-Time Urine Assay of Tenofovir in PrEP

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PROJECT SUMMARY/ ABSTRACT Three lessons of the pre-exposure prophylaxis (PrEP) clinical trials - that adherence is critical to effectiveness, that pharmacologic adherence measures are more reliable than self-report, and that a tool to measure adherence at the clinical point-of-care should improve adherence–must be addressed in order to interpret and optimize PrEP as it is rolled-out globally. Qualitative evidence from the PrEP trials, especially the VOICE study, where lack of adherence led to a finding of null efficacy for PrEP in young women not in serodiscordant couples in Africa, demonstrates that individuals on PrEP would find knowledge of their PrEP drug levels at a visit motivating for subsequent adherence. Moreover, there is ample evidence from other disease states that real-time monitoring of drug levels to the needed medication, followed by supportive feedback to the patient, increases adherence and improves outcomes. Our UCSF research group has helped pioneer the use of small hair samples (which are easy to collect, store and ship) to measure adherence to PrEP; other pharmacologic metrics of adherence to PrEP assess drug levels in plasma or dried blood spots. However, current methods to analyze PrEP drugs in any matrix, including urine, involve liquid chromatography/tandem- mass spectrometry (LC-MS/MS) which is expensive and cannot be performed in real-time. Our UCSF group, in collaboration with Alere Rapid Diagnostics, a company with vast expertise in developing point-of-care (POC) diagnostics, has now developed the first immunoassay (antibody-based assay) to quantitate TFV in urine, a matrix easily-accessible for POC testing. The immunoassay is highly sensitive (100%), sensitive (96%), and precise; TFV urine levels via the immunoassay are highly correlated with those from LC-MS/MS (r=0.95). Lateral flow immunoassays (LFA) allow for low-cost (<$2.00 per test) monitoring. Bringing together a highly experienced investigator team, this grant will leverage a directly- observed therapy study of TDF/FTC in Thailand to determine interpretive cut-offs for the assay to package the LFA into a clinically-useful, low-cost tool that indicates high, moderate, or low/no PrEP adherence (Aim 1). Aim 2 will examine the correlation of POC urine TFV levels with plasma TFV levels and HIV seroconversion events in a large completed trial (Partners PrEP). Aim 3 will evaluate the feasibility, acceptability, and impact of real- time monitoring/feedback using the POC assay on adherence over time among women on PrEP in Kenya. This proposal is highly innovative in that we have developed the first TFV immunoassay, allowing for POC adherence monitoring. This novel assay has further implications for HIV treatment. Since TFV-based regimens (TDF or tenofovir alafenamide (TAF)) are the backbone of HIV treatment, a low-cost POC TFV assay may help avert virologic failure and drug resistance between more expensive viral load measurements. This low-cost tool has the potential to improve PrEP and ART effectiveness during global expansion by both interpreting and enhancing adherence, aiding the quest to end new HIV infections worldwide.