1. 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.
- Author
-
Else LJ, Dickinson L, Edick S, Zyhowski A, Ho K, Meyn L, Dilly-Penchala S, Thompson B, Shaw V, Khoo S, and Brand RM
- Subjects
- Humans, Male, Adult, Female, Middle Aged, Pre-Exposure Prophylaxis methods, Young Adult, Plasma chemistry, Medication Adherence, Pyridones urine, Oxazines, Heterocyclic Compounds, 3-Ring pharmacokinetics, Heterocyclic Compounds, 3-Ring urine, Heterocyclic Compounds, 3-Ring blood, Heterocyclic Compounds, 3-Ring therapeutic use, Emtricitabine urine, Emtricitabine pharmacokinetics, Emtricitabine therapeutic use, Emtricitabine blood, Piperazines urine, Piperazines blood, Lamivudine urine, Lamivudine pharmacokinetics, Lamivudine blood, Point-of-Care Testing, HIV Infections drug therapy, Tenofovir urine, Tenofovir pharmacokinetics, Tenofovir therapeutic use, Tenofovir blood, Anti-HIV Agents urine, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents blood, Anti-HIV Agents therapeutic use
- 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)., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
- Published
- 2024
- Full Text
- View/download PDF