title: Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.
abstract: Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia, Modena, Italy. g.guaraldi@unimo.it
authors.forename: G
authors.initials: G
authors.lastname: Guaraldi
authors.forename: S
authors.initials: S
authors.lastname: Cocchi
authors.forename: M
authors.initials: M
authors.lastname: Codeluppi
authors.forename: F
authors.initials: F
authors.lastname: Di Benedetto
authors.forename: S
authors.initials: S
authors.lastname: Bonora
authors.forename: M
authors.initials: M
authors.lastname: Pecorari
authors.forename: W
authors.initials: W
authors.lastname: Gennari
authors.forename: N
authors.initials: N
authors.lastname: Cautero
authors.forename: A D
authors.initials: AD
authors.lastname: Pinna
authors.forename: G E
authors.initials: GE
authors.lastname: Gerunda
authors.forename: R
authors.initials: R
authors.lastname: Esposito
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active; D016903:Drug Monitoring / Q000379:methods*; D015658:HIV Infections / Q000188:drug therapy*; D006526:Hepatitis C / Q000601:surgery*; D006801:Humans; D017093:Liver Failure / Q000150:complications* / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents