title: Liver fibrosis progression in HIV-HCV-coinfected patients treated with distinct antiretroviral drugs and impact of pegylated interferon/ribavirin therapy.
abstract: BACKGROUND
  Advanced liver fibrosis frequently develops in patients with chronic hepatitis C coinfected with HIV. Non-invasive techniques for staging liver fibrosis, such as transient elastometry, may allow both periodic monitoring and examination of large patient populations.
  
  
  METHODS
  A programme of liver fibrosis assessment using transient elastometry has been ongoing at our institution since 2004. All HIV-HCV-coinfected patients having ≥2 examinations separated by >18 months were included. Liver fibrosis progression (LFP) was defined as an increase in liver stiffness from <9.5 kPa (Metavir F0-F2) to >9.5 kPa (Metavir F3-F4), or an increase >30% in patients with baseline Metavir F3-F4.
  
  
  RESULTS
  A total of 545 HIV-HCV-coinfected patients were analysed (mean age 41 years, 71% male, 81% intravenous drug users, mean body mass index 23.3 kg/m(2), 4.2% hepatitis B surface antigen-positive, 8.4% alcohol abuse, mean CD4(+) T-cell count 519 cells/μl). At baseline, 527 patients were on antiretroviral therapy, with the most frequent third drug being atazanavir (19.7%), efavirenz (15.9%), lopinavir (13.1%) or nevirapine (7.2%). A total of 99 (18%) patients experienced LFP during a mean (sd) follow-up of 70.9 (15.7) months. Use of protease inhibitors (OR 4.93, 95% CI 1.73, 14.0; P=0.03) and male gender (OR 5.12, 95% CI 1.37, 19.1; P=0.01) were associated with LFP. By contrast, the achievement of HCV clearance following pegylated interferon/ribavirin (PEG-IFN/RBV) therapy (OR 0.27, 95% CI 0.1, 0.79; P=0.02) was protective. Lopinavir exposure was significantly associated with LFP (OR 1.02, 95% CI 1.0, 1.04; P=0.03), whereas nevirapine was protective (OR 0.94, 95% CI 0.9, 0.99; P=0.02).
  
  
  CONCLUSIONS
  The use of protease inhibitors, mainly lopinavir, is associated with increased LFP in HIV-HCV-coinfected patients. By contrast, nevirapine therapy and, particularly, HCV clearance with PEG-IFN/RBV significantly reduce LFP.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: José V
authors.initials: JV
authors.lastname: Fernández-Montero
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Clara
authors.initials: C
authors.lastname: Sánchez-Parra
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012307:Risk Factors; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a