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

Investigator: Monica Gandhi, MD, MPH
Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): Kenya


 Pre-exposure prophylaxis (PrEP) with oral tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) prevents HIV infection, but measuring PrEP drug levels to assess adherence in the PrEP trials helped us understand that 1) drug levels measure adherence better than self-report; 2) many women in Africa at risk for HIV who are not in couples need help taking the PrEP pill every day; 3) measuring PrEP drug levels in the clinic and talking to the patient about adherence based on these results can help patients take PrEP drugs better. However, there is no current method to test PrEP drug levels on the spot because the available methods are complicated and involve expensive machines; our research group has now developed a way to measure adherence to TFV using an antibody-based test (“immunoassay”) in urine that can be performed cheaply at the point-of-care (POC) for individuals on TDF/FTC for either prevention or treatment. This study will work on packaging this immunoassay into a very easy-to-use, low-cost, clinical tool to identify adherence (high, moderate, no/low) to PrEP at the POC; examine the association between urine TFV levels and plasma TFV concentrations in a large completed trial of PrEP; and perform a pilot trial in women on PrEP in Kenya to see if measuring TFV in urine at the point-of-care is acceptable, easy-to-do, and leads to better adherence over time to this important HIV prevention pill.

hree 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.