Risk of Liver Enzyme Elevation During Treatment With Ritonavir-Boosted Protease Inhibitors Among HIV-Monoinfected and HIV/HCV-Coinfected Patients

Giuseppe Lapadula, Silvia Costarelli, Liliane Chatenoud, Francesco Castelli, Noemi Astuti, Simona Di Giambenedetto, Eugenia Quiros-Roldan, Laura Sighinolfi, Nicoletta Ladisa, Massimo Di Pietro, Alessia Zoncada, Elisa Di Filippo, Andrea Gori, Paola Nasta, Carlo Torti

Research output: Contribution to journalArticlepeer-review


Background: The risk of liver enzyme elevation (LEE) after different ritonavir-boosted protease inhibitors (PI/r) has not been fully assessed in real-life settings and in populations with high rates of hepatitis C virus (HCV) coinfection. Methods: Patients introducing a new PI/r between 1998 and 2012 were included, if transaminases and HCV antibody (Ab) were assessed before treatment initiation. Time to grade 3 and 4 LEE were assessed using univariable and multivariable conditional Cox analyses, stratified by HCV serostatus. Results: A total of 6193 HIV-infected patients (3242 HCV-Ab negative and 2951 HCV-Ab positive) were included. Incidence of grade 3 LEE was 1.05, 7.66, and 8.08 per 100 patient-years of followup among HCV-Ab negative, HCV-Ab-positive and HCV-RNA-positive patients, respectively. Among HCV-Ab-negative patients, no differences were detected between different PI/r. Use of darunavir/ritonavir was not associated with LEE among HCV-coinfected patients. Atazanavir/ritonavir use was associated with grade 3 LEE but only among HCV-Ab-positive patients (versus LPV/r, hazard ratio: 1.39; 95% confidence interval: 1.1 to 1.75). This risk was not confirmed in a subanalysis restricted to HCV-RNA-positive patients (versus LPV/r, hazard ratio: 1.16; 95% confidence interval: 0.87 to 1.55). Other independent predictors of grade 3 LEE among HCV-Ab-positive patients were older age, male gender, being treatment naive, nonnucleoside reverse transcriptase inhibitor coadministration, increased aspartate aminotransferase at baseline, overweight, positive HCV-RNA, and advanced estimated liver fibrosis. Conclusions: Occurrence of hepatotoxicity was a rare finding among HCV-Ab-negative patients and was not influenced by the type of PI/r. In particular, the use of darunavir/ritonavir, previously linked with severe cases of hepatotoxicity, was not associated with a greater risk of LEE, irrespective from HCV serostatus.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number3
Publication statusPublished - Jul 1 2015


  • atazanavir
  • boosted protease inhibitors
  • darunavir
  • hepatitis C virus
  • hepatotoxicity
  • liver toxicity
  • lopinavir
  • ritonavir
  • transaminases elevation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)


Dive into the research topics of 'Risk of Liver Enzyme Elevation During Treatment With Ritonavir-Boosted Protease Inhibitors Among HIV-Monoinfected and HIV/HCV-Coinfected Patients'. Together they form a unique fingerprint.

Cite this