Coadministration has not been studied. Rilpivirine is metabolized by CYP3A4 whereas cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Ursodeoxycholic acid is conjugated with glycine or taurine in the liver and secreted into bile. In vitro studies suggest that ursodeoxycholic acid is a CYP3A inducer. The literature reports the case of a patient on a stable ARV regimen of rilpivirine/emtricitabine/tenofovir alafenamide (25/200/25 mg once daily) who started treatment with ursodeoxycholic acid (300 mg twice daily). One month after initiating this treatment, rilpivirine trough concentrations became undetectable. Rilpivirine was replaced by darunavir/cobicistat and ursodeoxycholic acid treatment was maintained. Of interest, ursodeoxycholic acid did not significantly alter darunavir/cobicistat concentrations as the strong CYP3A4 inhibitor cobicistat may compensate for the inducing effect. This case suggests that ursodeoxycholic acid has the potential to alter the exposure of antiretrovirals which are metabolized by CYP3A4 but have no inhibitory properties, such as rilpivirine. Thus, until further data are available, we recommend that coadministration with rilpivirine should be avoided due to the risk of virological failure. No significant effect on cabotegravir is expected as there is no evidence that ursodeoxycholic acid induces UGT1A1 or UGT1A9.