Generic placeholder image

Current Clinical Pharmacology


ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

Review Article

Tenofovir Urine Assay to Monitor Adherence to HIV Pre-exposure Prophylaxis

Author(s): Ganesh S. Moorthy*, Linden Lalley-Chareczko, Helen C. Koenig and Athena F. Zuppa

Volume 15, Issue 2, 2020

Page: [102 - 104] Pages: 3

DOI: 10.2174/1574884714666191111125348


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. A semi-quantitative high-performance liquid chromatographymass 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. This assay was validated relative to other markers of adherence including dried blood spot and selfreport 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 of 50 young men who have sex with men (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. Further studies are underway to implement the tenofovir urine assay to monitor adherence and pre-exposure prophylaxis, nationally and internationally.

Keywords: Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF), HIV, Pre-Exposure Prophylaxis (PrEP), liquid chromatography-mass spectrometry, urine samples.

Next »
Graphical Abstract
Baeten JM, Donnell D, Ndase P, et al. Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367(5): 399-410.
[] [PMID: 22784037]
Grant RM, Lama JR, Anderson PL, et al. iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363(27): 2587-99.
[] [PMID: 21091279]
Anderson PL, Glidden DV, Liu A, et al. iPrEx Study Team. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med 2012; 4(151) 151ra125
[]] [PMID: 22972843]
Preexposure prophylaxis for the prevention of HIV infection in the United States clinical practice guideline 2014.
Organization WH. Consolidated guidelines on HIV preven-tion, diagnosis, treatment and care for key populations. Switzerland: Gene-va 2014.
Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: Clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 2004; 43(9): 595-612.
[] [PMID: 15217303]
Hawkins T, Veikley W, St Claire RL III, Guyer B, Clark N, Kearney BP. Intracellular pharmacokinetics of tenofovir diphosphate, carbovir triphosphate, and lamivudine triphosphate in patients receiving triple-nucleoside regimens. J Acquir Immune Defic Syndr 2005; 39(4): 406-11.
[] [PMID: 16010161]
Olds PK, Kiwanuka JP, Nansera D, et al. Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda. AIDS Care 2015; 27(3): 327-32.
[] [PMID: 25483955]
Koenig HC, Mounzer K, Daughtridge GW, et al. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis. HIV Med 2017; 18(6): 412-8.
[] [PMID: 28444867]
Lalley-Chareczko L, Clark D, Conyngham C, et al. Delivery of TDF/FTC for pre-exposure prophylaxis to prevent HIV-1 acquisition in young adult men who have sex with men and transgender women of color using a urine adherence assay. J Acquir Immune Defic Syndr 2018; 79(2): 173-8.
[] [PMID: 29905593]
Gandhi M, Bacchetti P, Rodrigues WC, et al. Development and validation of an immunoassay for tenofovir in urine as a real-Time metric of antiretroviral adherence. EClinicalMedicine 2018; 2-3: 22-8.
[] [PMID: 30906930]
Gandhi M, Bacchetti P, Spinelli IM, et al. Validation of a urine tenofovir immunoassay for adherence monitoring to PrEP and ART and establishing the cut-off for a point-of-care test. J Acquir Immune Defic Syndr 2019; 81(1): 72.
Pratt GW, Fan A, Melakeberhan B, Klapperich CM. A competitive lateral flow assay for the detection of tenofovir. Anal Chim Acta 2018; 1017: 34-40.
[] [PMID: 29534793]
Spinelli MA, Glidden DV, Rodrigues WC, et al. Low tenofovir level in urine by a novel immunoassay is associated with seroconversion in a preexposure prophylaxis demonstration project. AIDS 2019; 33(5): 867-72.
[] [PMID: 30649051]
Cohen SE, Sachdev D, Lee SA, et al. Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylax-is: A case report. Lancet HIV 2018.

© 2023 Bentham Science Publishers | Privacy Policy