title: Randomized trial comparing dose reduction and growth factor supplementation for management of hematological side effects in HIV/hepatitis C virus patients receiving pegylated-interferon and ribavirin.
abstract: BACKGROUND
  Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard treatment for hepatitis C virus (HCV) infection, are frequently associated with neutropenia and anemia, leading to high treatment discontinuation rates in HIV/HCV-coinfected patients. Our objective was to compare the effectiveness of intervening with hematologic growth factors versus dose reductions of standard HCV therapy for the management of treatment-induced hematologic disorders.
  
  
  METHODS
  Ninety-two HIV/HCV-coinfected, therapy-naive subjects received PEG-IFN alfa-2b 1.5 μg·kg⁻¹·wk⁻¹ and RBV 13 ± 2 mg·kg⁻¹·d⁻¹ for up to 48 weeks. Before treatment initiation, subjects were randomized to subsequently receive growth factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte colony-stimulating factor, or dose reduction (RBV and/or PEG-IFN) for anemia and neutropenia management, respectively. We analyzed the ability of each management strategy to control anemia and neutropenia and the percentage of subjects who achieved a successful treatment outcome according to the different management strategies.
  
  
  RESULTS
  During treatment, 43 subjects developed anemia (human erythropoietin, n = 24; dose reduction, n = 19), whereas 25 subjects developed neutropenia (granulocyte colony-stimulating factor, n = 10; dose reduction, n = 15). After the intervention, the increase in both hemoglobin and absolute neutrophil counts did not differ between the 2 side effect management strategies. Sustained response percentages were similar comparing anemic and neutropenic subjects regardless of management strategy (anemia: recombinant human erythropoietin, 29% versus dose reduction, 21%, P = 0.92; neutropenia: granulocyte colony-stimulating factor, 40% versus dose reduction, 20%, P = 0.46).
  
  
  CONCLUSIONS
  Growth factor supplementation and dose reduction do not seem to differ as management strategies for anemia and neutropenia in HIV/HCV-coinfected individuals treated with PEG-IFN/RBV.
authors.affiliation: Center for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. aht2002@med.cornell.edu
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Talal
authors.forename: Ruei-Chi
authors.initials: RC
authors.lastname: Liu
authors.forename: Marija
authors.initials: M
authors.lastname: Zeremski
authors.forename: Rositsa
authors.initials: R
authors.lastname: Dimova
authors.forename: Lorna
authors.initials: L
authors.lastname: Dove
authors.forename: Daniel
authors.initials: D
authors.lastname: Pearce
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.forename: Leleka
authors.initials: L
authors.lastname: Doonquah
authors.forename: David
authors.initials: D
authors.lastname: Aboulafia
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Hector
authors.initials: H
authors.lastname: Bonilla
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Galpin
authors.forename: Judy A
authors.initials: JA
authors.lastname: Aberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Johnston
authors.forename: Marshall J
authors.initials: MJ
authors.lastname: Glesby
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004921:Erythropoietin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b