Brief Report: Pharmacokinetics of Bictegravir and Tenofovir in Combination With Darunavir/Cobicistat in Treatment-Experienced Persons With HIV. (1st December 2021)

• Record Type: Journal Article
• Authors: Salama, Engie; Hill, Lucas; Patel, Nimish; Best, Brookie M.; Momper, Jeremiah D.
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 88:Number 4(2021)
• Publication Date: 2021-12-01
• Subjects: HIV -- pharmacokinetics -- darunavir -- tenofovir alafenamide -- bictegravir; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000002765
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : Background: Bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination (BIC/FTC/TAF 50/200/25 mg) is recommended as an initial regimen in patients who are antiretroviral (ARV)-naïve or virologically suppressed on a stable ARV regimen. However, no real-world pharmacokinetic (PK) data are available in treatment-experienced patients with antiretroviral resistance receiving BIC/FTC/TAF plus a boosted protease inhibitor. Setting/methods: This prospective, single-center, nonrandomized pharmacokinetic study enrolled adult treatment-experienced persons with HIV and creatinine clearance >30 mL/min receiving BIC/FTC/TAF + DRV/c as part of routine clinical care. Steady-state PK profiles of BIC, TAF, tenofovir (TFV), and DRV after daily dosing of BIC/FTC/TAF + darunavir/cobicistat (DRV/c) were obtained with samples at predose and 0.5, 1, 2, and 4 hours postdose. The AUC0–24 at steady state was extrapolated by imputing C0 for C24 for each participant (AUC0-tau, exp ). Results: Nine participants were enrolled with a median age of 59 years (range 54–67) and median number of years on ART of 19 (range 5.8–30). The median (interquartile range [IQR]) BIC AUC0-tau, exp and Cmax values were 128.9 µg*h/mL (78.1–159.5) and 6.9 µg/mL (5.1–9.8), respectively. The median (IQR) TAF AUC0-tau, exp and Cmax values were 0.376 µg*h/mL (0.199–0.430) and 0.276 µg/mL (0.149–0.543), respectively. Predose concentrations of TFV and DRV were comparable with historical data. Conclusion: Treatment-experienced persons with HIV receiving BIC/FTC/TAF + darunavir/cobicistat (DRV/c) had BIC exposures (AUC0-tau ) that were increased by approximately 26% compared with historical PK data. Although TAF exposures were substantially increased, plasma TFV was only modestly higher. These results suggest that BIC/TAF/FTC + DRV/c is a viable antiviral regimen option for treatment-experienced persons.