title: Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C.
abstract: BACKGROUND
  Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency.
  
  
  METHODS
  Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry.
  
  
  RESULTS
  A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 micro g/mL for NVP (35 patients), 2.8 micro g/mL for EFV (46 patients), 5.8 micro g/mL for LPV (56 patients), 0.4 micro g/mL for ATV (58 patients), and 0.7 micro g/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 micro g/mL; P<.01) and NVP (median, 6.6 vs. 5.8 micro g/mL; P=.33). EFV plasma levels above the toxic threshold (>4 micro g/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P<.001). The same trend was seen for NVP levels >8 micro g/mL (50% vs. 27%; P=.27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis.
  
  
  CONCLUSIONS
  Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Rodríguez-Novoa
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Andrés
authors.initials: A
authors.lastname: Ruiz
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jiménez-Nácher
authors.forename: Luz
authors.initials: L
authors.lastname: Martín-Carbonero
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D061466:Lopinavir; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D010078:Oxazines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D010078:Oxazines; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019829:Nevirapine; C098320:efavirenz; D019438:Ritonavir