PROJECT SUMMARY Adequate adherence to combination antiretroviral therapy (ART) is required to suppress HIV viral loads among individuals living with HIV, which is essential both for individual-level benefits and to prevent the onward transmission of HIV. While newer ART regimens are better tolerated, have fewer side effects and a lower risk of drug resistance than older regimens, treatment success nevertheless remains dependent on patient adherence. Current approaches to identify inadequate adherence are either subjective or insensitive, whereas objective markers of treatment exposure (drug levels) in hair, dried blood spots or plasma require expensive instrumentation and are therefore not scalable. As the ultimate aim of treatment is to achieve HIV viral load suppression, use of HIV viral load testing is being expanded worldwide. As it remains an expensive test, it is often performed infrequently and therefore treatment failure is detected late, resulting in missed opportunities to improve adherence. A low-cost point-of-care (POC) assay to assess adherence to ART, objectively at clinic visits, in resource limited settings (RLS), could: 1) Provide immediate information on recent adherence which can then be followed with appropriate adherence support; 2) Allow for more frequent assessment of adherence and reinforcement of appropriate adherence behavior before virologic failure occurs; 3) Differentiate patients with virological failure due to poor adherence from those with drug resistance. Finally, with the current roll-out of tenofovir, lamivudine and dolutegravir (TLD) in RLS, failure rates are expected to be low and resistance rare, necessitating a monitoring strategy primarily focused on identifying patients with inadequate adherence. Recently the University of California, San Francisco (UCSF) Hair Analytical Laboratory and Abbott™ Rapid Diagnostics has developed a urine-based immunoassay for tenofovir (TFV). This antibody-based assay detects the presence of TFV in urine accurately, is easy-to-perform, and is both low-cost (< $2 dollars per test) and point- of-care (POC), which allows for immediate adherence feedback to both patient and provider. We will therefore conduct a study with the following aims: 1) Investigate the ability of the urine-based tenofovir rapid assay (UTRA) to detect virologic failure in a cross-sectional study, along with the association of UTRA with self-reported adherence and long term TFV exposure as measured in dried blood spots (120 patients); 2) Qualitatively assess the acceptability of UTRA in patients (25) and health care workers (5); 3) Perform a pilot randomized controlled study among adherence-challenged patients to investigate the usefulness, feasibility and acceptability of UTRA-supported adherence counseling, compared to standard of care counseling, to impact long-term HIV viral load outcomes (100 patients in each arm). The envisaged overall impact is that by study end, we hope to have validated this novel real-time urine-based treatment adherence monitoring tool, in a resource- limited setting, and inform a larger trial to trigger immediate adherence support and ration more expensive laboratory testing, using the practical POC test, to improve long-term virologic outcomes worldwide.

PROJECT NARRATIVE Adherence to combination antiretroviral therapy is required to suppress patient HIV viral loads, which is essential to both optimize individual health and prevent onward transmission of HIV. We therefore propose to investigate a novel urine-based point-of-care assay that detects the presence of tenofovir, the backbone of most antiretroviral regimens worldwide, to detect inadequate adherence and support adherence. Our objectives are to study the ability of this new assay to identify patients in need of adherence support and its usefulness, feasibility and acceptability when used to reinforce and support treatment adherence.