Drug interactions involving human immunodeficiency virus protease inhibitors are common due to their inhibition of the cytochrome P450 3A4 isoenzyme. We describe the case of an HIV-infected patient treated with ritonavir-boosted darunavir who developed cushingoid features following an intra-articular injection of triamcinolone acetate. We review the probable mechanism for this interaction and describe similar cases of Cushing syndrome in patients receiving concomitant ritonavir and triamcinolone.