Co-administration with rifampicin is contraindicated due to the effect of rifampicin on the bictegravir component of Biktarvy. 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). The interaction has not been studied with tenofovir alafenamide. Co-administration of rifampicin may decrease tenofovir alafenamide plasma concentrations.

Biktarvy is contraindicated to be coadministered with rifampin due to decreased bictegravir plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to Biktarvy. Coadministration of rifampin (600 mg once daily) and bictegravir (75 mg single dose) decreased bictegravir Cmax and AUC by 28% and 75%.

INSIGHT was an open-label, phase-2b randomised controlled trial in ART-naive or non-naive adults with HIV and TB taking a rifampicin-based TB regimen (for <8 weeks). Participants were randomised 2:2 to the bictegravir arm (BIC/FTC/TAF) or a standard of care dolutegravir arm (DTG/3TC/TDF) with BIC/FTC/TAF or DTG dosed twice daily until 2 weeks post-TB treatment and once daily thereafter, until 48 weeks. Overall, 122 participants were enrolled: 80 in the BIC and 42 in the DTG arm. Coadministration of twice daily BIC/FTC/TAF and rifampicin resulted in geometric mean bictegravir AUC of 0.376 (90% CI 0.335-0.422), Cmax of 0.466 (90% CI 0.421-0.515) and Ctrough of 0.217 (90% CI 0.179-0.263). Despite an ~80% reduction in bictegravir Ctrough with rifampicin coadministration, average Ctrough remained 3.1-fold above the protein adjusted 95% effective trough concentration (inhibitory quotient, 0.162 mg/L). None of the Ctrough values following directly observed dosing were below the inhibitory quotient, while pre-dose concentrations following unobserved doses were below inhibitory quotient (11.8% during TB treatment and 3.8 % after TB treatment). At week 48, HIV VL was <50 copies/mL in 76/80 (95%) participants.

A PK sub-study nested within the INSIGHT trial evaluated the plasma and intracellular PK of tenofovir (TFV) and TFV-diphosphate (TFV-DP) in HIV/TB co-infected adults initiated on a bictegravir/emtricitabine/TAF regimen dosed twice-daily until 2 weeks post rifampicin-based TB treatment and once daily thereafter until 48 weeks. Plasma and dried blood spot samples were collected at weeks 4 and 12 during TB treatment and at week 32 after TB treatment. Overall, 43 participants were enrolled in the PK sub-study with a median (IQR) age of 35 (30-39) years and weight of 57 (52-64) kg; 77% were male and all were black. Geometric mean ratio (90% CI) AUC0-24h for TFV was 1.24 (1.06, 1.45) and 1.21 (1.03, 1.42) at weeks 4 and 12 on TAF twice daily with rifampicin relative to week 32 on TAF once daily. GMR AUC0-24h for TFV-DP was 0.97 (0.79, 1.19) at week 12 versus week 32 with and without rifampicin, respectively. Overall, 95% of participants achieved viral suppression at week 24 in the bictegravir arm. TAF twice daily + rifampicin did not result in higher FTV-DP intracellular concentrations than for once daily dosing. There were no bictegravir/emtricitabine/TAF related drug toxicity events. The authors concluded that twice daily TAF achieved sufficient exposures to overcome rifampicin induction in HIV/TB co-infected adults, achieving TFV-DP intracellular concentrations above those previously reported with TDF.

The effect of rifampicin (600 mg once daily) on the pharmacokinetics of bictegravir when administered twice daily (bictegravir/emtricitabine/tenofovir 50/200/25 mg, twice daily postprandial, for 28 days) was investigated in two cohorts of HIV-negative subjects (n=26 per cohort). Cohort 1 received bictegravir/emtricitabine/tenofovir alone while cohort 2 received the same plus rifampicin. Coadministration reduced bictegravir AUC, Cmax and Ctrough by approximately 61%, 47% and 80%, respectively. The authors note that although bictegravir Ctrough decreased by ~80%, trough concentrations in all subjects were above the protein adjusted EC95 of 162 ng/ml. They conclude that administering bictegravir twice daily with rifampicin did not mitigate the enzyme inducing effect of rifampicin sufficiently to replicate the Ctrough concentrations seen in phase three bictegravir clinical trials.