title: Reduced raltegravir clearance in HIV-infected liver transplant recipients: an unexpected interaction with immunosuppressive therapy?
abstract: OBJECTIVE
  Liver transplantation (LTx) is considered a safe procedure in selected HIV-infected patients. In this clinical setting raltegravir is the antiretroviral of choice due to its optimal tolerability and its negligible interactions with immunosuppressive drugs. We aimed at providing data on the pharmacokinetics of raltegravir in LTx recipients, on which the available information is inconclusive.
  
  
  METHODS
  In this retrospective multicentre study we characterized the pharmacokinetics of raltegravir in a consecutive series of HIV-infected LTx recipients referred to our laboratory for therapeutic drug monitoring (TDM) and compared the obtained profiles with those collected from a control group of HIV-infected patients.
  
  
  RESULTS
  Seventeen HIV-infected LTx patients were considered. LTx recipients had significantly higher raltegravir AUC0-12 compared with the control group of HIV-infected patients [14 314 (11 627-19 998) versus 8795 (5218-12 954) ng·h/mL; P < 0.01]. Two LTx patients experienced moderate increments in serum transaminases, nausea and vomiting that improved after raltegravir dose reduction.
  
  
  CONCLUSIONS
  High raltegravir exposure and acceptable safety profile were observed in HIV-infected LTx recipients. Our results highlight that some patients may obtain an advantage from TDM-guided raltegravir dose adjustments with potential benefits in terms of drug tolerability.
authors.affiliation: Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.affiliation: Division of Infectious Diseases, AO Ospedale Niguarda Ca' Granda, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.affiliation: Department of Infectious Diseases, L. Sacco University Hospital, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sollima
authors.affiliation: Division of Infectious Diseases, AO Ospedale Niguarda Ca' Granda, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moioli
authors.affiliation: Infectious Diseases Department, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Caterina Uberti
authors.initials: CU
authors.lastname: Foppa
authors.affiliation: Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.affiliation: Clinical Pharmacology Unit, CNR Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università di Milano, 20157 Milan, Italy Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.affiliation: Department of Infectious Diseases, L. Sacco University Hospital, Milan, Italy cristina.gervasoni@unimi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasoni
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010949:Plasma / Q000737:chemistry; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D000637:Transaminases / Q000097:blood; D066027:Transplant Recipients
chemical_list: D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D000068898:Raltegravir Potassium; D000637:Transaminases