Tenofovir urine assay to monitor adherence to HIV pre-exposure prophylaxis (PrEP).

Abstract

BACKGROUND Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are prodrugs of tenofovir and have excellent long-term efficacy and tolerability for the treatment of HIV. An objective marker of adherence to tenofovir-based therapy could be clinically useful in supporting adherence to TDF-based HIV pre-exposure prophylaxis (PrEP) in populations in whom self-report has been shown to be unreliable, and could play a role in resource-limited settings to support HIV and hepatitis B treatment adherence. METHODS A semi-quantitative high-performance liquid chromatography-mass spectrometry method for tenofovir quantification of urine samples was developed. This assay detects tenofovir concentration in log10 levels between 1 and 10,000 ng/mL, and was shown to distinguish between recent adherence and low/non-adherence to both TDF and TAF, with a concentration of >1000 ng/mL highly predictive of medication ingestion in the last 24-48 hours. RESULTS This assay was validated relative to other markers of adherence including dried blood spot and self-report in a highly adherent population of PrEP patients, and tenofovir was shown to be stable at room temperature in urine for at least 14 days. The assay was successfully used in a clinical setting to maintain high PrEP adherence and retention in care in 50 young men who have sex with me (MSM) over 48 weeks, to assess PrEP adherence in youth with mental health conditions, and to monitor drug levels relative to plasma levels in a case study of chewed TDF/FTC (tenofovir/emtricitabine) for PrEP. CONCLUSION The findings of this review confirm the utility of tenofovir urine assay to monitor adherence to HIV pre-exposure prophylaxis. Further studies are underway to implement the tenofovir urine assay to monitor adherence and pre-exposure prophylaxis, nationally and internationally.