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A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation.
Aaron S Devanathan1, Amanda J Poliseno2, Nicole R White2
1University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
Journal of Acquired Immune Deficiency Syndromes (1999)
|January 15, 2025
Summary
Accurate adherence monitoring for tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is crucial. Measuring drug metabolites in dried blood spots provides the most accurate assessment of stable and changing adherence patterns.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- HIV Therapeutics Adherence Research
Background:
- Incomplete adherence to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) compromises treatment effectiveness.
- Adherence biomeasures, such as drug metabolite concentrations, offer superior accuracy compared to self-reported adherence.
- Investigating novel blood matrices for quantifying intracellular metabolites like tenofovir-diphosphate (TFVdp) and FTC-triphosphate (FTCtp) is essential for optimizing adherence estimation.
Purpose of the Study:
- To evaluate different blood matrices for measuring TFVdp and FTCtp to improve adherence estimation for TDF/FTC.
- To compare the accuracy of moderate-term and long-term adherence biomeasures.
- To identify the optimal blood matrix for predicting stable and changing adherence patterns.
Main Methods:
- Employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify TFVdp and FTCtp in dried blood spots, microsamples, packed cell layers, and peripheral blood mononuclear cells (PBMCs).
- Utilized noncompartmental analysis to estimate pharmacokinetic parameters like half-lives and accumulation ratios.
- Developed regression models to determine drug concentration thresholds associated with specific dosing frequencies (<4 and ≥4 doses/week).
Main Results:
- Terminal half-life estimates differentiated moderate-term (FTCtp, TFVdp in PBMCs) from long-term (TFVdp in red blood cell matrices) measures.
- Model-derived thresholds accurately classified adherence over 14- and 28-day periods (81%-91% and 82%-85%, respectively) when both metabolites were considered.
- Dried blood spots demonstrated the highest accuracy (74%-94%) in predicting stable adherence and moderate accuracy (42%-47%) for changing adherence patterns.
Conclusions:
- Moderate-term adherence biomeasures are more accurate for classifying adherence over 14 days than long-term measures over 28 days.
- Combining moderate- and long-term biomeasures enhances the prediction of both stable and dynamic adherence patterns.
- Dried blood spots represent the most accurate matrix for assessing adherence to TDF/FTC.
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