Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
Pharmacokinetics of Twice-daily Tenofovir Alafenamide in Adults With HIV-associated Tuberculosis on Bictegravir/Emtricitabine/Tenofovir Alafenamide and Rifampicin.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание 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.
Osuala Emmanuella Chinonso, Nkuhairwe Ivan Nicholas, Letsoalo Marothi Peter, Naidoo Kogieleum, Perumal Rubeshan, Rooney James F, Wiesner Lubbe, Wasmann Roeland E, Denti Paolo, Dooley Kelly E, Naidoo Anushka, INSIGHT Study Team
Аннотация
BACKGROUND: Tenofovir alafenamide (TAF) is a key component of many fixed-dose combinations used to treat HIV. There are limited data on the pharmacokinetics of plasma TAF, tenofovir (TFV), or intracellular tenofovir diphosphate (TFV-DP), among people with HIV (PWH) and tuberculosis (TB) who are taking rifampicin-based TB treatment.
METHODS: Participants in the intervention arm of the INSIGHT trial (NCT04734652) receiving bictegravir/emtricitabine/TAF (BIC/FTC/TAF 50/200/25 mg) were enrolled into the semi-intensive pharmacokinetic substudy. BIC/FTC/TAF was administered twice-daily during rifampicin-based TB treatment (∼24 weeks) and once-daily thereafter. Plasma (TAF/TFV) and dried blood spot samples (TFV-DP) were collected at weeks 4 and 12 (predose, 1, 2, 4, 6, and 8-12 hours postdose) during TB treatment and at week 32 (predose, 1, 2, 4, 6-8 and 24-25 hours postdose) post-TB treatment. Pharmacokinetic parameters were determined using noncompartmental analysis. Clinical and safety data were collected.
RESULTS: Among 43 participants enrolled; median (IQR) age and weight were 35 (30-39) years and 58 (52-65) kg; 77% were male. Geometric least square mean ratios (90% CI) at week 12 (twice-daily TAF) relative to week 32 (once-daily TAF) for TAF AUC0-4, TFV, and TFV-DP AUC0-24 were 1.55 (1.13-2.13), 1.24 (1.07-1.44), and 1.32 (1.13-1.53), respectively. At week 24, 95% of participants achieved viral suppression, with no treatment-related serious adverse events or drug discontinuations.
CONCLUSIONS: Twice-daily TAF was safe and efficacious and achieved similar exposures of intracellular TFV-DP in PWH taking rifampicin for TB compared to once-daily TAF taken alone. These data support the use of TAF in a fixed-dose combination of BIC/FTC/TAF during rifampicin-containing TB treatment.
METHODS: Participants in the intervention arm of the INSIGHT trial (NCT04734652) receiving bictegravir/emtricitabine/TAF (BIC/FTC/TAF 50/200/25 mg) were enrolled into the semi-intensive pharmacokinetic substudy. BIC/FTC/TAF was administered twice-daily during rifampicin-based TB treatment (∼24 weeks) and once-daily thereafter. Plasma (TAF/TFV) and dried blood spot samples (TFV-DP) were collected at weeks 4 and 12 (predose, 1, 2, 4, 6, and 8-12 hours postdose) during TB treatment and at week 32 (predose, 1, 2, 4, 6-8 and 24-25 hours postdose) post-TB treatment. Pharmacokinetic parameters were determined using noncompartmental analysis. Clinical and safety data were collected.
RESULTS: Among 43 participants enrolled; median (IQR) age and weight were 35 (30-39) years and 58 (52-65) kg; 77% were male. Geometric least square mean ratios (90% CI) at week 12 (twice-daily TAF) relative to week 32 (once-daily TAF) for TAF AUC0-4, TFV, and TFV-DP AUC0-24 were 1.55 (1.13-2.13), 1.24 (1.07-1.44), and 1.32 (1.13-1.53), respectively. At week 24, 95% of participants achieved viral suppression, with no treatment-related serious adverse events or drug discontinuations.
CONCLUSIONS: Twice-daily TAF was safe and efficacious and achieved similar exposures of intracellular TFV-DP in PWH taking rifampicin for TB compared to once-daily TAF taken alone. These data support the use of TAF in a fixed-dose combination of BIC/FTC/TAF during rifampicin-containing TB treatment.