{"doi":"10.1093/jac/dkae147","title":"Tenofovir, emtricitabine, lamivudine and dolutegravir concentrations in plasma and urine following drug intake cessation in a randomized controlled directly observed pharmacokinetic trial to aid point-of-care testing","abstract":"BACKGROUND: Poor adherence to ART and pre-exposure prophylaxis (PrEP) can impact patient and public health. Point-of-care testing (POCT) may aid monitoring and adherence interventions. OBJECTIVES: We report the pharmacokinetics of tenofovir [dosed as tenofovir disoproxil (TDF) and tenofovir alafenamide (TAF)], emtricitabine (FTC), lamivudine (3TC) and dolutegravir (DTG) in plasma and urine following drug cessation to evaluate adherence targets in urine for POCT. METHODS: Subjects were randomized (1:1) to receive DTG/FTC/TAF or DTG/3TC/TDF for 15 days. Plasma and spot urine were collected on Day 15 (0-336 h post final dose). Drug concentrations were quantified using LC-MS, and non-linear mixed-effects models applied to determine drug disposition between matrices and relationship with relevant plasma [dolutegravir protein-adjusted 90% inhibitory concentration (PA-IC90 = 64 ng/mL) and minimum effective concentration (MEC = 324 ng/mL)] and urinary thresholds [tenofovir disoproxil fumarate 1500 ng/mL]. RESULTS: Of 30 individuals enrolled, 29 were included (72% female at birth, 90% Caucasian). Median (range) predicted time to plasma dolutegravir PA-IC90 and MEC were 83.5 (41.0-152) and 49.0 h (23.7-78.9), corresponding to geometric mean (90%) urine concentrations of 5.42 (4.37-6.46) and 27.4 ng/mL (22.1-32.7). Tenofovir in urine reached 1500 ng/mL by 101 h (58.6-205) with an equivalent plasma concentration of 6.20 ng/mL (4.21-8.18). CONCLUSIONS: These data support use of a urinary tenofovir threshold of <1500 ng/mL (tenofovir disoproxil fumarate-based regimens) as a marker of three or more missed doses for a POCT platform. However, due to low dolutegravir concentrations in urine, POCT would be limited to a readout of recent dolutegravir intake (one missed dose).","journal":"Journal of Antimicrobial Chemotherapy","year":2024,"id":448652,"datarank":0.31593710057624225,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.04717318019203397,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.04717318019203397,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04302896"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1267611,"name":"Laura Dickinson","orcid":"0000-0001-5557-9396","position":1,"is_corresponding":false},{"id":1072593,"name":"Stacey Edick","orcid":null,"position":2,"is_corresponding":false},{"id":1268049,"name":"Ashley Zyhowski","orcid":null,"position":3,"is_corresponding":false},{"id":644588,"name":"Ken Ho","orcid":"0000-0001-7973-1268","position":4,"is_corresponding":false},{"id":292427,"name":"Leslie A. Meyn","orcid":"0000-0001-7723-9878","position":5,"is_corresponding":false},{"id":831636,"name":"Sujan Dilly‐Penchala","orcid":null,"position":6,"is_corresponding":false},{"id":1267612,"name":"Beth Thompson","orcid":"0009-0006-2467-1935","position":7,"is_corresponding":false},{"id":1267613,"name":"Victoria Shaw","orcid":"0000-0002-0429-0186","position":8,"is_corresponding":false},{"id":254199,"name":"Saye Khoo","orcid":"0000-0002-2769-0967","position":9,"is_corresponding":false},{"id":446538,"name":"Rhonda M. Brand","orcid":null,"position":10,"is_corresponding":false},{"id":21589,"name":"Laura Else","orcid":"0009-0007-0078-3294","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T02:02:12.215092Z","pmid":"38758205","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":[]}