Randomized Trial to Optimize Virologic Suppression Rates Using a Point-of-Care Urine Monitoring Assay (ROVING-PUMA)

About This Grant

PROJECT SUMMARY/ ABSTRACT Although World Health Organization (WHO) guidelines now recommend once‐daily tenofovir‐lamivudine‐ dolutegravir (TLD) for antiretroviral therapy (ART), adherence challenges in taking daily oral ART persist. The rates of virologic suppression (VS) worldwide for those on ART are around 70%, with a lower rate (65%) approximately three years after starting ART. Pharmacologic adherence metrics, where ART levels are directly measured in a biomatrix ‐ such as plasma, urine, dried blood spots (DBS), or hair‐ reflect actual pill‐taking and predict virologic suppression more accurately than self‐reported adherence. Our UCSF research group has helped pioneer the use of small hair samples to measure adherence to ART, but most methods to analyze ART drugs in any matrix involve liquid chromatography/tandem‐mass spectrometry (LC‐MS/MS) which is expensive and cannot be performed in real‐time. Point‐of‐care (POC) adherence monitoring requires the development of a highly selective antibody and subsequent development of an immunoassay to ART. Evidence from other disease states show 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 group has now developed one of the first immunoassays (antibody‐based assay) to detect tenofovir (TFV) in urine, a matrix easily‐accessible for point‐of‐care testing. Work by our team among people with HIV (PWH) in Namibia assessed the effect of the urine assay on VS rates among persistently virally non‐ suppressed adults on ART, despite the application of WHO‐recommended enhanced adherence counseling (EAC). In a pre‐post analysis, we found that VS rates increased from 0% to 92% after urine testing and counseling at monthly ART refills over six months. Now is the time to perform a large, randomized trial to explore the ability of counseling informed by results from the urine TFV assay to increase VS versus standard‐of‐care EAC to provide evidence for incorporating the urine POC test into clinical practice. Aim 1 of this renewal R01 application proposes a large randomized trial (n=500) comparing use of the POC urine test for TFV with tailored counseling versus standard‐of‐care EAC among participants with documented virologic failure on TLD at clinics in South Africa. The primary outcome is VS at six months; secondary outcomes include assessing the sustainability of the 6‐month intervention on VS out to 24 months; development of viral resistance in each arm; and positive urine tests by arm. Aim 2 examines implementation outcomes including acceptability and feasibility, with Aim 3 assessing cost‐effectiveness of the intervention. If the trial is successful, we will have demonstrated that an easy‐to‐use inexpensive POC urine adherence test will increase VS among populations with virologic failure on TLD, which will benefit patients, decrease the development of viral resistance, and prevent forward transmission. The aspiration of this grant is to move the low‐cost urine assay into clinical care and inform WHO ART guidelines (WHO letter of support included).