التفاصيل البيبلوغرافية
| العنوان: |
Brief Report: Validation of a Urine Tenofovir Immunoassay for Adherence Monitoring to PrEP and ART and Establishing the Cutoff for a Point-of-Care Test. |
| المؤلفون: |
Gandhi, Monica MD, MPH (AUTHOR), Bacchetti, Peter PhD (AUTHOR), Spinelli, Matthew A. MD (AUTHOR), Okochi, Hideaki PhD (AUTHOR), Baeten, Jared M. MD, PhD (AUTHOR), Siriprakaisil, Oraphan MD (AUTHOR), Klinbuayaem, Virat MD (AUTHOR), Rodrigues, Warren C. MS (AUTHOR), Wang, Guohong PhD (AUTHOR), Vincent, Michael MS (AUTHOR), Cressey, Tim R. PhD (AUTHOR), Drain, Paul K. MD (AUTHOR) |
| المصدر: |
JAIDS: Journal of Acquired Immune Deficiency Syndromes. 5/1/2019, Vol. 81 Issue 1, p72-77. 6p. |
| مستخلص: |
Background: Current pharmacologic adherence monitoring for antiretrovirals involves expensive, labor-intensive liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based methods. Antibody-based assays can monitor and support adherence in real time. We developed a tenofovir (TFV)-based immunoassay and further validated it in a directly observed therapy (DOT) study. Design: Pharmacologic DOT study of TFV disoproxil fumarate (TDF)/emtricitabine (FTC) administered to HIV-noninfected volunteers. Methods: The TARGET study provided directly observed TDF 300 mg/FTC 200 mg 7 (high adherence), 4 (moderate), and 2 doses/week (low) to 30 volunteers (10/group) in Thailand, collecting a total of 637 urine samples over 6 weeks of administration and during washout. ELISA measured urine TFV levels by the immunoassay and LC-MS/MS-based concentrations served as the gold standard. A mixed-effects regression model evaluated cutoffs for a point-of-care assay. Performance characteristics of the immunoassay were compared with LC-MS/MS at a chosen cutoff. Results: Median TFV levels were 12,000 ng/mL by the immunoassay 1 day after dosing; 5000 ng/mL 2 days after dosing; 1500 ng/mL 3 days after dosing; and below the lower limit of quantification thereafter (>=4 days). An immunoassay cutoff of 1500 ng/mL accurately classified 98% of patients who took a dose 24 hours ago as adherent. The specificity and sensitivity of the immunoassay compared with LC-MS/MS at the 1500 ng/mL cutoff were 99% and 94%; the correlation between TFV levels by the 2 assays was high (0.92, P < 0.00001). Conclusions: We have developed a novel TFV immunoassay that is highly specific, sensitive, and correlates strongly with LC-MS/MS measurements in a large DOT study. Adherence benchmarks from this DOT study will guide the development of a low-cost rapid point-of-care test for pre-exposure prophylaxis and antiretroviral treatment adherence monitoring and interventions. [ABSTRACT FROM AUTHOR] |
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