title: The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon.
abstract: OBJECTIVE
  To study the association between trough ribavirin concentration (C(trough)) with sustained virological response (SVR) and haemoglobin (Hb) decrease in HIV/hepatitis C virus (HCV)-co-infected (HIV+/HCV+) patients treated with anti-HCV therapy.
  
  
  METHODS
  HIV+/HCV+ patients treated with ribavirin and pegylated interferon were prospectively evaluated. Qualitative and quantitative HCV-RNA, Hb levels and ribavirin C(trough) were measured at baseline and weeks 2, 4, 12, 24, 36 and 48 during therapy. HCV-RNA was also measured at 24 weeks after the end of therapy. Efficacy analysis was performed on patients with a definitive virological outcome (SVR, relapser and non-responder), whereas for toxicity analysis, dropouts were considered until the last available observation.
  
  
  RESULTS
  Fifty-two patients (54.7% with genotype 1 or 4) were included. Overall, no correlation between ribavirin C(trough) and early virological response (EVR) nor SVR was found. However, in patients with genotype 1 or 4, ribavirin C(trough) was independently associated with EVR (P = 0.036) and SVR (P = 0.046). A ribavirin C(trough) cut-off of 1600 ng/mL was found to be associated with both EVR (chi(2) = 5.69, P = 0.028) and SVR (chi(2)=4.2, P = 0.04). Higher ribavirin C(trough) correlated with Hb decrease (R = -0.361, P = 0.009) and was independently associated with an Hb decrease of >4 g/dL (P = 0.009). Receiver operating characteristic (ROC) analysis indicated that a ribavirin C(trough) of >2300 ng/mL was associated with an Hb decrease of >4 g/dL (chi(2) = 8.08, P = 0.01).
  
  
  CONCLUSIONS
  Our study confirmed a relationship between ribavirin exposure and both efficacy and toxicity. Moreover, we found ribavirin C(trough) cut-offs for both SVR in genotypes 1 and 4 and overall haematological toxicity. These findings deserve further clinical evaluation.
authors.affiliation: Department of Infectious Diseases, University of Turin, Turin, Italy. diego.agui@libero.it
authors.forename: D
authors.initials: D
authors.lastname: Aguilar Marucco
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez de Requena
authors.forename: S
authors.initials: S
authors.lastname: Bonora
authors.forename: C
authors.initials: C
authors.lastname: Tettoni
authors.forename: M
authors.initials: M
authors.lastname: Bonasso
authors.forename: T
authors.initials: T
authors.lastname: De Blasi
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
authors.forename: M
authors.initials: M
authors.lastname: Sciandra
authors.forename: M
authors.initials: M
authors.lastname: Siccardi
authors.forename: L
authors.initials: L
authors.lastname: Baietto
authors.forename: L
authors.initials: L
authors.lastname: Trentini
authors.forename: A
authors.initials: A
authors.lastname: Sinicco
authors.forename: G
authors.initials: G
authors.lastname: Cariti
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D010949:Plasma / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000627:therapeutic use* / Q000633:toxicity; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a