Effect of coadministered HIV-protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipients

Abstract

A patient with human immunodeficiency virus infection and end-stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half-life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV-1 protease inhibitors. © 2009 Société Française de Pharmacologie et de Thérapeutique.