Pharmacokinetic Interaction Between Amprenavir/Ritonavir and FosAmprenavir on Cyclosporine in Two Patients With Human Immunodeficiency Virus Infection Undergoing Orthotopic Liver Transplantation G. Guaraldi, S. Cocchi, M. Codeluppi, F. Di Benedetto, S. Bonora, A. Motta, K. Luzi, M. Pecorari, W. Gennari, M. Masetti, G.E. Gerunda, and R. Esposito ABSTRACT The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C trough ) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C trough of 5293 ng/mL and RTV C trough of 186 ng/mL. Forty-eight hours after initiation of HAART, C trough of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C trough of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C trough of CsA was around 600 ng/mL and C trough of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity. T HE CURRENT USE of highly active antiretroviral therapy (HAART) has greatly enhanced overall life expectancy for patients with human immunodeficiency virus (HIV). It has changed the natural history of HIV infec- tion. Presently the leading cause of death among these patients is chronic hepatitis B and C coinfections, which have been acquired due to the same risk factors as HIV. 1 Thus, orthotopic liver transplantation (OLT) is a rational therapeutic option for selected HIV-infected patients who have concomitant end-stage liver disease (ESLD). 2,3 Drug– drug interactions between HAART and immuno- suppressives represent crucial points in HIV management of post-OLT patients: protease inhibitors (PI) and non- nucleoside reverse transcriptase inhibitors are key elements of HAART. They are known to inhibit the cytochrome P450 3A enzyme system, which is also responsible for the metab- olism of immunosuppressive drugs, such as cyclosporine (CsA), tacrolimus, and Sirolimus. 4–6 Thus, given the com- plex pharmacological interactions between the PIs and From the Department of Internal Medicine and Medical Spe- cialties (G.G., S.C., M.C., A.M., K.L., R.E.), Infectious Diseases Clinic, University of Modena and Reggio Emilia, Modena, Italy; Liver and Multivisceral Transplant Center (F.D.B., M.M., G.E.G.), University of Modena and Reggio Emilia, Modena, Italy; Depart- ment of Infectious Diseases (S.B.), University of Torino, Torino, Italy; and Center for Diagnosis of Viral Diseases (M.P., W.G.), University of Modena and Reggio Emilia, Modena, Italy. Address reprint requests to Giovanni Guaraldi, MD, Depart- ment of Internal Medicine and Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia School of Medicine, Via del Pozzo 71, 41100 Modena, Italy. E-mail: g.guaraldi@unimo.it 0041-1345/06/$–see front matter © 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2006.02.013 360 Park Avenue South, New York, NY 10010-1710 1138 Transplantation Proceedings, 38, 1138 –1140 (2006)