Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels

We present the case of a patient with hepatitis C-induced cirrhosis and con comitant human immunodeficiency virus infection who underwent orthotopic li ver transplantation. The patient developed severe, prolonged tacrolimus tox icity in the presence of human immunodeficiency virus protease inhibitors. At various times, the patient received saquinavir, ritonavir, and nelfinavi r in conjunction with tacrolimus. In each instance, the tacrolimus concentr ation rose to toxic levels. We hypothesize that the protease inhibitors' co mpetition for binding to cytochrome P450 isoenzyme system CYP3A induced ext reme prolongation of tacrolimus metabolism. After stabilization of the pati ent, reinstitution of treatment with nelfinavir resulted in a >95% reductio n in tacrolimus dosing from 4 mg twice per day to 0.5 mg once every 3-5 day s.