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.


Else, Laura J, Dickinson, Laura ORCID: 0000-0001-5557-9396, Edick, Stacey, Zyhowski, Ashley, Ho, Ken, Meyn, Leslie, Dilly-Penchala, Sujan, Thompson, Beth ORCID: 0009-0006-2467-1935, Shaw, Victoria ORCID: 0000-0002-0429-0186, Khoo, Saye ORCID: 0000-0002-2769-0967 et al (show 1 more authors) (2024) 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. The Journal of antimicrobial chemotherapy, 79 (7). pp. 1597-1605. ISSN 0305-7453, 1460-2091

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Abstract

<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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].<h4>Results</h4>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).<h4>Conclusions</h4>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).

Item Type: Article
Uncontrolled Keywords: Plasma, Humans, HIV Infections, Oxazines, Piperazines, Pyridones, Heterocyclic Compounds, 3-Ring, Lamivudine, Anti-HIV Agents, Adult, Middle Aged, Female, Male, Medication Adherence, Young Adult, Pre-Exposure Prophylaxis, Tenofovir, Emtricitabine, Point-of-Care Testing
Depositing User: Symplectic Admin
Date Deposited: 06 Sep 2024 15:53
Last Modified: 08 Dec 2024 23:22
DOI: 10.1093/jac/dkae147
Open Access URL: https://doi.org/10.1093/jac/dkae147
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3184350
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