cabotegravir + rifabutin

Cabotegravir + rifabutin refers to the co-administration of two small molecule drugs: cabotegravir, an integrase strand transfer inhibitor (INSTI) used primarily for HIV-1 infection, and rifabutin, a rifamycin antibiotic used as an alternative to rifampin for treatment of tuberculosis, including in HIV coinfected individuals. The combination is clinically relevant for people with HIV who require tuberculosis treatment, since rifabutin is a moderate inducer of drug-metabolizing enzymes and has less impact on cabotegravir exposures compared to rifampin, but still modestly reduces cabotegravir levels. While oral cabotegravir can be co-administered with rifabutin without dose adjustment, injectable cabotegravir (long-acting) should generally be avoided with rifabutin due to insufficient evidence on safe dosing adjustments and potential loss of efficacy. The mechanistic interaction is driven by rifabutin’s induction of UGT1A1-mediated cabotegravir metabolism. Cabotegravir is primarily developed for HIV-1 infection, including as long-acting injectable forms, while rifabutin is used for tuberculosis therapy and prevention.