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. Coadministration of rifampicin (600 mg once daily) and bictegravir (75 mg single dose) decreased bictegravir AUC and Cmax by 75% and 28% (due to induction of CYP3A, UGT1A1, 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 daily rifapentine (600 mg) plus isoniazid (300 mg) (1HP) on bictegravir trough concentration and virologic response was evaluated in people living with HIV with latent TB infection. Bictegravir trough concentrations after 1HP initiation were determined in 48 study participants. The percentage of bictegravir trough concentrations above the protein adjusted EC95 (162 ng/mL) were 65% on day 15 and 35% on day 29 post 1HP initiation. Viral loads were below 200 and 50 copies/mL in 100% and 98% of the enrolled participants before initiation of 1HP; 92% and 73% on day 15; 98% and 92% on day 29 and 100% and 98% 3 months after 1HP discontinuation. Bictegravir concentrations were significantly decreased with the concurrent use of 1HP therefore coadministration is not recommended.

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.