Date of report 23 Sep 2025
Reported case interaction between
Bictegravir and Rifabutin
Bictegravir and Rifabutin
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Rifabutin 300 mg
Pyrazinamide 1500 mg
Moxifloxacine 400 mg
Ethambutol 1200 mg
Haloperidol (2 mg/mL) 10 drops x 2
Cotrimozaxole every other day
Subcutaneous insulin: rapid (8 + 16 + 16 units) and slow (35 units at night)
Clinical case description
A 72-year-old female patient was admitted for disseminated isoniazide-resistant tuberculosis.
In her past medical history, we listed hypertension, dyslipidemia, type 2 diabetes, and HIV infection (known for approximately 7 years). She had discontinued antiretroviral treatment several times due to cultural and psychological issues with accepting the infection and its treatment. At the time of presentation her HIV RNA was 3810 copies/mL and her CD4 cell count was 181 cells/mm3.
Anti-tubercular treatment was started with rifampicin/ethambutol/pyrazinamide/moxifloxacin. After 2 weeks, the reinitiation of antiretroviral treatment was advised, but the patient refused. After an etno-psychological consult she accepted but agreed on a 2-pill maximum treatment, and we decided to start tenofovir alafenamide/emtricitabine/bictegravir (B/F/TAF) twice daily. After one week, we measured bictegravir trough concentration and it was 67 ng/mL, much lower than expected. After questioning, she admitted having taken B/F/TAF only one pill once a day; she rfused to take it twice daily and to change to double dose dolutgravir.
We then decided to leave B/F/TAF and switch rifampicin to rifabutin (300 mg/day). After 2 weeks we measured bicetgravir trough levels and they were in range (2360 ng/mL). She continued taking rifabutin/pyrazinamide/ethambutol/moxifloxacin and B/F/TAF: three months later HIV RNA was undetctable and CD4 cell count was 356 cells/mm3.
Clinical Outcome
Editorial Comment
This is an interesting case. A significant interaction is expected because rifabutin reduces bictegravir (BIC) trough levels, although the clinical relevance remains uncertain. Where therapeutic drug monitoring (TDM) is available, these data support the once-daily use of B/F/TAF in complex patients such as this one.
Rifampicin is a strong inducer of CYP3A4 and UGT1A1, producing a marked reduction in bictegravir exposure and a high risk of virologic failure when coadministered with B/F/TAF. The strategy of prescribing B/F/TAF twice daily in the presence of rifampicin is off-label, supported by limited evidence, and carries uncertain efficacy and potential safety concerns. In this case, subtherapeutic bictegravir levels confirmed that risk. An alternative approach endorsed in guidelines is double-dose dolutegravir, but this also poses challenges, including variable pharmacokinetics, gastrointestinal intolerance, and reduced adherence.
Despite coadministration of B/F/TAF and rifabutin is not recommended, switching rifampicin to rifabutin could be considered a safer option, since rifabutin is a weaker inducer and allows bictegravir to achieve therapeutic concentrations, though monitoring for hematological toxicity and potential drug–drug interactions is required.
This case highlights several key points: the clinical importance of induction effects on integrase inhibitors, the limitations of unvalidated dose-adjustment strategies, and the utility of TDM to guide individualized treatment decisions. Long-term follow-up with both pharmacokinetic and virologic monitoring will be essential to further validate this approach.
University of Liverpool Recommendation
These drugs should not be coadministered
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