Coadministration is not recommended as it may significantly decrease elvitegravir/cobicistat plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Coadministration of elvitegravir/cobicistat (150 mg/150 mg once daily) and rifabutin (300 mg once daily alone or 150 mg every other day with elvitegravir/cobicistat) decreased elvitegravir Cmin by 67%. Rifabutin exposure was similar to values obtained alone, but 25-O-desacetylrifabutin exposures were 4.8 to 6.3 fold higher. The European SPC suggests that if the combination is needed, to use rifabutin 150 mg 3 times per week on set days (e.g. Monday-Wednesday-Friday) with increased monitoring for rifabutin associated adverse reactions including neutropenia and uveitis due to increased desacetyl rifabutin exposure. Further dose reduction of rifabutin has not been studied and a twice weekly dose of 150 mg may not provide an optimal exposure to rifabutin leading to a risk of rifamycin resistance and a treatment failure. Rifabutin could decrease the exposure of tenofovir alafenamide (induction of intestinal transporters). However, a drug-drug interaction study demonstrated that coadministration of emtricitabine/tenofovir alafenamide (200/25 mg once daily) and rifampicin (600 mg once daily) in healthy volunteers gave intracellular tenofovir-DP exposures which were 4.2-fold higher than those achieved by standard dose tenofovir-DF alone (300 mg once daily).