title: Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin.
abstract: Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 microg/kg for 1 week, 1.5 microg/kg for 3 weeks, and 1.0 microg/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 microg/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 +/- 0.86 log vs. 5.15 +/- 1.04 log). The 3-microg/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-microg/kg dose during the first 48 hours (2.08 +/- 0.93 log vs. 1.09 +/- 0.80 log; P <.001) and both increased at 72 hours (0.54 +/- 0.73 log vs. 0.03 +/- 0.36 log; P = not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 +/- 0.99 log vs. 0.72 +/- 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance.
authors.affiliation: Liver Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. mbuti@hg.vhebron.es
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanchez-Avila
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Carlos
authors.initials: C
authors.lastname: Stalgis
authors.forename: Auristela
authors.initials: A
authors.lastname: Valdés
authors.forename: Maria
authors.initials: M
authors.lastname: Martell
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a