Co-administration is not recommended due to the expected decrease of tenofovir alafenamide. Coadministration of rifabutin (300 mg once daily) and bictegravir (75 mg once daily) decreased bictegravir AUC, Cmin and Cmax by 38%, 56% and 20%, respectively (due to induction of CYP3A and P-gp). The interaction has not been studied with tenofovir alafenamide. Co-administration of rifabutin may decrease tenofovir alafenamide plasma concentrations.

Coadministration may decrease concentrations of bictegravir and tenofovir alafenamide. Coadministration with rifabutin is not recommended. Coadministration of rifabutin (300 mg once daily) and bictegravir (75 mg once daily) decreased bictegravir Cmax, AUC and Cmin by 20%, 38% and 56%, respectively.

Bictegravir Ctrough and viral load were evaluated in a prospective multi-centre study enrolling people with HIV on rifabutin containing regimen and bictegravir/emtricitabine/tenofovir alafenamide for at least 28 days. The primary endpoint was the proportion of bictegravir Ctrough levels above the protein adjusted 95% effective concentration (PA-EC95: 162 ng/mL). Between October 2023 and June 2025, 18 people with HIV (median age 41 years (IQR: 33-50), 94.4% men; 28% had HIV RNA below 50 copies/mL and 11% CD4 counts above 200 cells/mm3) received rifabutin containing therapy together with bictegravir/emtricitabine/tenofovir alafenamide. During rifabutin co-administration, bictegravir Ctrough level decreased significantly to 438.3 ng/mL (IQR 400-781) compared with 3261 ng/mL (IQR 1957-4696) without rifabutin representing a median reduction Ctrough reduction of 86% (IQR 72-90%). Despite this substantial decrease, only one (5.6%) participant had a bictegravir Ctrough level below 162 ng/mL but the participant remained virologically suppressed. During one-year of follow-up of concurrent use of rifabutin and bictegravir/emtricitabine/tenofovir alafenamide, the proportion of participants achieving plasma HIV viral loads below 50 copies/mL increased progressively: 50% at month 1, 62% at month 3, 86% at month, and 100% at months 9 and 12. The authors concluded that despite the significant reduction in bictegravir Ctrough levels, people with HIV receiving concurrent rifabutin can achieve and maintain viral suppression over one year of follow-up, with adequate bictegravir Ctrough levels for effective HIV control.