{"doi":"10.17615/0zzz-7758","title":"A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation","abstract":"Background: Incomplete adherence to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) reduces effectiveness. Adherence biomeasures (i.e. drug concentrations in biological specimen) are more accurate than self-report. TDF/FTC’s intracellular active metabolites (tenofovir-diphosphate; TFVdp and FTC-triphosphate; FTCtp) can be quantified in different types of blood samples to estimate adherence. To optimize adherence estimation, we investigated approaches to measure TFVdp and FTCtp in four blood matrices. Methods: Twelve HIV-negative, healthy volunteers were enrolled in a single center, open-label, 3-phase, directly observed therapy study. LC-MS/MS methods quantified TFVdp/FTCtp in dried blood spots, volumetrically accurate microsampling, upper layer packed cells and peripheral blood mononuclear cells (PBMCs). Non-compartmental analysis estimated half-lives and accumulation ratios. Correlations characterized relationships between clinical variables and exposure. Regression models were fit to determine concentrations associated with <4 and ≥4 doses/week; correct classification percentages were determined. Results: Terminal half-life estimates of 3-4 vs 15-22 days distinguished between moderate-term (FTCtp in all samples; TFVdp in PBMCs) versus long-term (TFVdp in red blood cell-containing matrices) measures. Model-derived thresholds accurately categorized <4 and ≥4 doses/week when including both metabolites for 14- and 28-day dosing periods (81-91% and 82-85%, respectively). Within each classification and regression trees analyses containing both moderate- and long-term measures, dried blood spots exhibited highest accuracy to predict stable (74-94%) and changing (42-47%) adherence patterns. Conclusion: We demonstrate higher accuracy of moderate-term biomeasures to classify adherence over a 14-day period compared to long-term biomeasures to classify adherence over a 28-day period. Combined moderate- and long-term biomeasures predicted stable and changing adherence patterns, with dried blood spots exhibiting highest accuracy.","journal":"UNC Libraries","year":2025,"id":582900,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536629,"name":"Julie B. Dumond","orcid":"0000-0002-3500-5819","position":1,"is_corresponding":false},{"id":429937,"name":"Aaron S. Devanathan","orcid":"0000-0002-2778-3725","position":2,"is_corresponding":false},{"id":370691,"name":"Amanda P. Schauer","orcid":"0000-0002-7026-7224","position":3,"is_corresponding":false},{"id":926858,"name":"Ann Marie Weideman","orcid":"0000-0002-1653-9102","position":4,"is_corresponding":false},{"id":370688,"name":"Mackenzie L. Cottrell","orcid":"0000-0002-0291-5111","position":5,"is_corresponding":false},{"id":1075049,"name":"Amanda Poliseno","orcid":"0009-0006-0150-0500","position":6,"is_corresponding":false},{"id":429938,"name":"Nicole White","orcid":"0000-0002-5741-8008","position":7,"is_corresponding":false},{"id":130929,"name":"Michael G. Hudgens","orcid":"0000-0002-9106-4194","position":8,"is_corresponding":false},{"id":375127,"name":"Craig Sykes","orcid":null,"position":9,"is_corresponding":false},{"id":299313,"name":"Kayla W. Kilpatrick","orcid":"0000-0002-8678-9000","position":10,"is_corresponding":false},{"id":346803,"name":"Elias P. Rosen","orcid":"0000-0001-5531-7281","position":11,"is_corresponding":false},{"id":249715,"name":"Cynthia L. Gay","orcid":"0000-0002-3620-3059","position":12,"is_corresponding":false},{"id":370695,"name":"Angela D. M. Kashuba","orcid":"0000-0002-9171-8493","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}