Co-administration is not recommended. The interaction has not been studied with any of the components of Biktarvy. Co-administration of rifapentine may decrease bictegravir and tenofovir alafenamide plasma concentrations (due to induction of CYP3A and P-gp).

Coadministration may decrease concentrations of bictegravir and tenofovir alafenamide. Coadministration with rifapentine is not recommended. Coadministration of rifampin (600 mg once daily) and bictegravir (75 mg single dose) decreased bictegravir Cmax and AUC by 28% and 75%.

The effect of once-weekly rifapentine on the pharmacokinetics of bictegravir/emtricitabine/tenofovir alafenamide was evaluated in 30 HIV-negative volunteers. Participants received bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) once daily on days 1-8 followed by a washout period from days 9-14. Participants received subsequently bictegravir/emtricitabine/tenofovir alafenamide once daily on days 15-30 with rifapentine once-weekly (weight adjusted dosing) co-dosed on days 15, 22 and dosed 12 hours before bictegravir/emtricitabine/tenofovir alafenamide on day 29. Bictegravir trough samples were collected on days 16-21 and 23-29 between rifapentine doses to examine time-course of induction. Rifapentine once-weekly decreased bictegravir AUC by 15% (co-dosed) and 26% (12 h apart) and Cmin by 40% (co-dosed) and 57% (12 h apart). Importantly, bictegravir Cmin decreased as low as 83% by day 4 post rifapentine dosing. Bictegravir Cmin did not return back to steady-state concentrations between rifapentine doses. A 12 h staggered administration of rifapentine resulted in a more pronounced decline in bictegravir Cmin compared to co-administration. No clinically significant changes in the pharmacokinetics of emtricitabine, tenofovir alafenamide, tenofovir and tenofovir diphosphate were observed upon coadministration with rifapentine. All treatments were well-tolerated. Given the significant decline in bictegravir Cmin following administration of rifapentine, the use of bictegravir/emtricitabine/tenofovir alafenamide is not recommended with the weekly administration of rifapentine.