title: Early monitoring of ribavirin plasma concentrations may predict anemia and early virologic response in HIV/hepatitis C virus-coinfected patients.
abstract: Ribavirin (RBV) in combination with pegylated interferon alpha (pegIFN) is currently the standard treatment of hepatitis C virus (HCV) infection. The development of anemia requires a reduction in RBV doses in a substantial proportion of patients, limiting their chances of treatment response. The primary goal of this study was to assess if early monitoring of RBV plasma levels could help to predict anemia as well as early HCV RNA response in HIV/HCV-coinfected individuals. The secondary goal was to evaluate if antiretroviral drugs might influence RBV plasma levels. Plasma RBV concentrations were measured at weeks 4 and 12 in 98 HIV/HCV-coinfected individuals who initiated therapy with pegIFN-2a (180 microg/wk) plus RBV (800-1200 mg/d). RBV plasma levels correlated with RBV dose per kilogram of body weight (P = 0.02). Larger drops in hemoglobin levels were independently associated with higher RBV plasma levels and zidovudine (ZDV) use (P < 0.001). Likewise, higher RBV levels (P = 0.007) and HCV genotype 3 (P < 0.001) were found to be independent predictors of virologic response at week 4. Similar findings were obtained at week 12. Patients receiving ZDV concomitantly showed significantly higher RBV plasma concentrations compared with those who did not (3.28 mug/mL vs. 2.51 mug/mL; P = 0.002). RBV levels were not significantly altered by the coadministration of other nucleoside/nucleotide analogues. In summary, RBV plasma levels correlate with the development of anemia and with the achievement of an early virologic response. Therefore, early therapeutic drug monitoring might help to tailor RBV dosages, improving the efficacy and safety of anti-HCV treatment.
authors: Pharmacy Service, Hospital Carlos III, Madrid, Spain.
authors: Ana Lucía
authors: AL
authors: Rendón
authors: Marina
authors: M
authors: Núñez
authors: Miriam
authors: M
authors: Romero
authors: Pablo
authors: P
authors: Barreiro
authors: Luz
authors: L
authors: Martín-Carbonero
authors: Javier
authors: J
authors: García-Samaniego
authors: Inmaculada
authors: I
authors: Jiménez-Nácher
authors: Juan
authors: J
authors: González-Lahoz
authors: Vincent
authors: V
authors: Soriano
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016014:Linear Models; D008297:Male; D012254:Ribavirin / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D012254:Ribavirin