Twice-daily bictegravir does not overcome drug interaction with rifampicin

Polly Clayden, HIV i-Base

Twice daily dosing of bictegravir is not sufficient to mitigate the induction effect of rifampicin and still achieve adequate bictegravir concentrations.

Results from a drug-drug interaction study of bictegravir (BIC) and rifampicin (RIF) conducted in HIV negative participants were included in an oral presentation at CROI 2018.

BIC is primarily eliminated by the drug metabolising enzymes CYP3A and UGT1A1. RIF is well-known to be a potent inducer of metabolising enzymes.

A previous study looking at once daily coadministration of the two drugs showed a reduction in BIC concentrations of approximately 75%. This study evaluated the pharmacokinetics (PK) of BIC given twice daily with RIF.

The was a phase 1, open label study with a parallel design. Participants were enrolled into one of two cohorts – 26 per cohort.

Cohort 1 participants received the fixed dose combination BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for 28 days. Cohort 2 participants received B/F/TAF twice daily plus RIF 600 mg once daily, for 28 days.

Intensive sampling was performed on day 28. Statistical comparisons for BIC used geometric least squares mean (GLSM) ratios and associated 90% confidence intervals with B/F/TAF once daily as reference.

This evaluation found BIC AUC0-24h and Cmax were decreased approximately 61% and 47%, respectively, versus B/F/TAF once daily alone.

BIC Ctrough GLSM was approximately 80% lower, as compared with that with B/F/TAF once daily.

These findings showed that twice daily administration of B/F/TAF with RIF does not mitigate the induction effect sufficiently to give BIC Ctrough concentrations associated with the B/F/TAF registrational phase 3 studies.


Simple HIV and TB co-treatment is essential for low- and middle-income countries so if BIC cannot be administered with RIF this is one reason to suggest this is not good candidate for optimised ART. 


Custodio JM et al. Pharmacokinetics of bictegravir administered twice daily in combination with rifampin. 25th CROI. Boston. 4–7 March 2018.
 Oral abstract 34. (abstract) (webcast)

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