The Journal of antimicrobial chemotherapy · 2025
Cellular pharmacology of tenofovir alafenamide and emtricitabine in neutrophils and platelets in people with and without HIV.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mainella Vincent A, Branchford Brian, Nemkov Travis, Hosford Seth, Coyle Ryan P, Johnson Bethany, Choi Ye Ji, Williams Martin, Zheng Jia-Hua, Bushman Lane, Kiser Jennifer J, Anderson Peter L, Brooks Kristina M
Аннотация
BACKGROUND: Previous studies have primarily focused on nucleos(t)ide reverse transcriptase inhibitor pharmacology in peripheral blood mononuclear cells (PBMCs) and erythrocytes via dried blood spots (DBS), but not other major blood cells.
OBJECTIVES: Our objectives were to describe and compare the concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in DBS, PBMCs, neutrophils, and platelets in people with HIV (PWH) and people without HIV (PWOH).
METHODS: DBS, PBMCs, neutrophils, and platelets were isolated from whole blood drawn from PWH and PWOH receiving tenofovir alafenamide and emtricitabine. TFV-DP and FTC-TP concentrations were quantified using LC-MS/MS in each cell type. Linear regression models controlled for time on drug, adherence, and time since last dose, where applicable, to determine geometric mean percent differences (95% confidence interval) by HIV status and estimated half-lives.
RESULTS: Data were available in 13 PWH (96% male) and 30 PWOH (53% male). Compared with PWOH, TFV-DP in DBS was 48.9% (15.6%, 91.9%) higher and FTC-TP in platelets was 36.3% (4.5%, 77.7%) higher; TFV-DP in platelets also trended higher [43.5% (-3.24%, 113%)]. No other cell types significantly differed by HIV status. TFV-DP and FTC-TP demonstrated the longest half-lives in neutrophils, followed by PBMCs and then platelets. After normalizing to cell volume, both drugs accumulated from greatest to least in PBMCs, neutrophils, platelets, and erythrocytes across both PWH and PWOH.
CONCLUSIONS: Our findings highlight differential drug disposition across cell types that also vary by serostatus in DBS and platelets. The mechanisms and implications of these findings require additional research.
OBJECTIVES: Our objectives were to describe and compare the concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in DBS, PBMCs, neutrophils, and platelets in people with HIV (PWH) and people without HIV (PWOH).
METHODS: DBS, PBMCs, neutrophils, and platelets were isolated from whole blood drawn from PWH and PWOH receiving tenofovir alafenamide and emtricitabine. TFV-DP and FTC-TP concentrations were quantified using LC-MS/MS in each cell type. Linear regression models controlled for time on drug, adherence, and time since last dose, where applicable, to determine geometric mean percent differences (95% confidence interval) by HIV status and estimated half-lives.
RESULTS: Data were available in 13 PWH (96% male) and 30 PWOH (53% male). Compared with PWOH, TFV-DP in DBS was 48.9% (15.6%, 91.9%) higher and FTC-TP in platelets was 36.3% (4.5%, 77.7%) higher; TFV-DP in platelets also trended higher [43.5% (-3.24%, 113%)]. No other cell types significantly differed by HIV status. TFV-DP and FTC-TP demonstrated the longest half-lives in neutrophils, followed by PBMCs and then platelets. After normalizing to cell volume, both drugs accumulated from greatest to least in PBMCs, neutrophils, platelets, and erythrocytes across both PWH and PWOH.
CONCLUSIONS: Our findings highlight differential drug disposition across cell types that also vary by serostatus in DBS and platelets. The mechanisms and implications of these findings require additional research.