Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C.
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.
Barreiro
Pablo
P
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Rodríguez-Novoa
Sonia
S
Labarga
Pablo
P
Ruiz
Andrés
A
Jiménez-Nácher
Inmaculada
I
Martín-Carbonero
Luz
L
Gonzalez-Lahoz
Juan
J
Soriano
Vincent
V
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
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