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.