The Pediatric infectious disease journal · 2025
Pharmacokinetics of Tenofovir Diphosphate, Lamivudine Triphosphate and Emtricitabine Triphosphate in Adolescents With HIV Infection With and Without Tuberculosis Coinfection.
СтатьяНазвание и аннотация: Перевод в очереди
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Antwi Sampson, Enimil Anthony, Yang Hongmei, Martyn-Dickens Charles, Dompreh Albert, Amissah Aikins Kofi, Ojewale Oluwayemisi, Bosomtwe Dennis, Sly-Moore Eugenia, Asiedu Priscilla, Frimpong Appiah Augustina, Opoku Theresah, Sarfo Ama D, Bushman Lane R, Ellison Lucas, Alghamdi Wael A, Anderson Peter L, Kwara Awewura
Аннотация
BACKGROUND: There is limited data on the cellular pharmacokinetics (PK) of the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in adolescents with HIV (AWH). We examined the steady-state concentrations of the NRTIs anabolites in dried blood spots (DBS) and peripheral blood mononuclear cells (PBMCs) in AWH and those with tuberculosis (TB) confection on rifampin-containing TB treatment.
METHODS: AWH and TB/HIV coinfection on TB treatment receiving tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/lamivudine (3TC) 300 mg or emtricitabine (FTC) 200 mg daily for at least 8 weeks were enrolled. DBS were collected at the study entry. Following 2 weeks of telephone adherence reminders, DBS sampling was repeated, and 4 PBMC samples were collected between 10 and 20 hours postdose. Concentrations of TFV diphosphate (TFV-DP), 3TC triphosphate and FTC triphosphate in DBS and PBMCs were measured. Adherence based on TFV-DP concentrations in DBS and the anabolites concentrations in DBS and PBMCs were compared by TB coinfection status, and ≤14 versus >14 years old.
RESULTS: Of 52 participants (46.2% with TB), the median (interquartile range) age 15.0 (14.5-17.0) years, 25 (48.1%) were male. Adherence based on TFV-DP in DBS was not significantly different by TB coinfection status or age group. The concentrations of the anabolites in DBS and PBMCs were similar in AWH and TB/HIV coinfection and ≤14 versus >14 years of age; and median concentrations at the population level were similar to historical values in adults.
CONCLUSIONS: The concentrations of the recommended NRTIs and pharmacokinetics-determined adherence were not significantly different in adolescents with TB or younger age.
METHODS: AWH and TB/HIV coinfection on TB treatment receiving tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/lamivudine (3TC) 300 mg or emtricitabine (FTC) 200 mg daily for at least 8 weeks were enrolled. DBS were collected at the study entry. Following 2 weeks of telephone adherence reminders, DBS sampling was repeated, and 4 PBMC samples were collected between 10 and 20 hours postdose. Concentrations of TFV diphosphate (TFV-DP), 3TC triphosphate and FTC triphosphate in DBS and PBMCs were measured. Adherence based on TFV-DP concentrations in DBS and the anabolites concentrations in DBS and PBMCs were compared by TB coinfection status, and ≤14 versus >14 years old.
RESULTS: Of 52 participants (46.2% with TB), the median (interquartile range) age 15.0 (14.5-17.0) years, 25 (48.1%) were male. Adherence based on TFV-DP in DBS was not significantly different by TB coinfection status or age group. The concentrations of the anabolites in DBS and PBMCs were similar in AWH and TB/HIV coinfection and ≤14 versus >14 years of age; and median concentrations at the population level were similar to historical values in adults.
CONCLUSIONS: The concentrations of the recommended NRTIs and pharmacokinetics-determined adherence were not significantly different in adolescents with TB or younger age.