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  • Title: Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C.
    Author: Barreiro P, Rodríguez-Novoa S, Labarga P, Ruiz A, Jiménez-Nácher I, Martín-Carbonero L, Gonzalez-Lahoz J, Soriano V.
    Journal: J Infect Dis; 2007 Apr 01; 195(7):973-9. PubMed ID: 17330787.
    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.
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