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.
J Antimicrob Chemother
; 79(7): 1597-1605, 2024 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-38758205
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 (11) to receive DTG/FTC/TAF or DTG/3TC/TDF for 15â days. Plasma and spot urine were collected on Day 15 (0-336â 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-IC90â=â64â ng/mL) and minimum effective concentration (MECâ=â324â ng/mL)] and urinary thresholds [tenofovir disoproxil fumarate 1500â 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 49.0â h (23.7-78.9), corresponding to geometric mean (90%) urine concentrations of 5.42 (4.37-6.46) and 27.4â ng/mL (22.1-32.7). Tenofovir in urine reached 1500â ng/mL by 101â h (58.6-205) with an equivalent plasma concentration of 6.20â ng/mL (4.21-8.18).CONCLUSIONS:
These data support use of a urinary tenofovir threshold of <1500â 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).
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Banco de datos:
MEDLINE
Asunto principal:
Oxazinas
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Piperazinas
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Piridonas
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Infecciones por VIH
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Lamivudine
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Fármacos Anti-VIH
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Tenofovir
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Emtricitabina
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Pruebas en el Punto de Atención
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Compuestos Heterocíclicos con 3 Anillos
Idioma:
En
Año:
2024
Tipo del documento:
Article