title: Liver enzyme elevation during darunavir-based antiretroviral treatment in HIV-1-infected patients with or without hepatitis C coinfection: data from the ICONA foundation cohort.
abstract: OBJECTIVE
  To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen.
  
  
  METHODS
  HIV-infected patients enrolled in the Italian Cohort of Naïve to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative). Time to LEE endpoint was defined using the ACTG toxicity scale, based on changes relative to baseline. Kaplan-Meier was used to estimate 1-year and 2-year probability of LEE. The incidence rate ratios (IRRs) of LEEs were estimated until the last follow-up (intention-to-treat analysis [ITT]) and up to darunavir/ritonavir discontinuation (on-treatment analysis [OT]).
  
  
  RESULTS
  Overall, 703 patients were included. Ninety-one were HCV-Ab positive; of those, 68 (9.7%) had active HCV coinfection. In 879 person-years of follow-up, 101 LEEs occurred (ITT). No severe hepatotoxicity event was registered in active HCV coinfected patients. HCV active coinfection was predictive of LEE in the overall population (OT: adjusted incidence rate ratio (IRR), 2.25; 95% CI, 0.70-7.24; P = .17; ITT: adjusted IRR, 3.62; 95% CI, 1.67-7.83; P < .001) and in naïve patients (OT: adjusted IRR, 6.29; 95% CI, 2.54-15.55; P = .00; ITT: adjusted IRR, 3.87; 95% CI, 0.99-15.16; P = .05).
  
  
  CONCLUSIONS
  No grade 3-4 LEEs occurred in HCV active coinfected patients. HCV active coinfected patients experienced low grade LEEs more frequently than HCV-Ab negative patients. Darunavir/ritonavir seems to be safe whatever the HCV status, when liver enzymes are carefully monitored.
authors.affiliation: Clinica Malattie Infettive, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: Clinica Malattie Infettive, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
authors.forename: Laura Ambra
authors.initials: LA
authors.lastname: Nicolini
authors.affiliation: INMI L Spallanzani, Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lorenzini
authors.affiliation: Malattie Infettive Azienda Ospedaliera Niguarda Ca' Grande, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.affiliation: INMI L Spallanzani, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: UCL Research Department of Infection and Population Health, London, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Malattie Infettive Azienda Ospedaliera Universitaria San Gerardo, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.affiliation: Clinica Malattie Infettive Università di Chieti, Chieti, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Vecchiet
authors.affiliation: Clinica Malattie Infettive Università di Modena, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Clinica Malattie Infettive Università di Tor Vergata, Roma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.affiliation: Clinica Malattie Infettive, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
authors.affiliation: Clinica Malattie Infettive Ospedale San Paolo, Università di Milano, Milano, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.lastname: For The Icona Foundation Study Group
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D000069454:Darunavir; D004338:Drug Combinations; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV; darunavir; hepatitis C virus; hepatotoxicity; liver enzyme elevations; ritonavir