Pharmacokinetics of bictegravir and tenofovir in combination with darunavir/cobicistat in treatment-experienced persons with HIV.

BACKGROUND Bictegravir co-formulated with tenofovir alafenamide and emtricitabine as a fixed-dose combination (BIC/FTC/TAF 50/200/50 mg) is recommended as an initial regimen in patients who are antiretroviral (ARV)-naive 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, non-randomized 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, TFV and DRV following daily dosing of BIC/FTC/TAF + DRV/c were obtained with samples at pre-dose and 0.5, 1, 2 and 4 hours post-dose. 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 (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 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 were 0.376 µg*h/mL (0.199 - 0.430) and 0.276 µg/mL (0.149 - 0.543), respectively. Pre-dose concentrations of TFV and DRV were comparable to historical data. CONCLUSION Treatment-experienced persons with HIV receiving BIC/FTC/TAF + DRV/c had BIC exposures (AUC0-tau) that were increased by approximately 26% compared to 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.