title: Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1-infected patients.
abstract: Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection. Individually tailored reduction in treatment duration in HCV type 1-infected patients represents one possible strategy. Four hundred thirty-three patients were randomly assigned to receive either 1.5 microg/kg peginterferon alfa-2b weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an individually tailored treatment duration (18-48 weeks; n = 208, group B). In the latter group, treatment duration was calculated using the time required to induce HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL) multiplied by the factor 6. All bDNA negative samples were retested with the more sensitive transcription-mediated amplification (TMA) assay (sensitivity limit, 5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7% versus 14.2% [P< 0.0005]). Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment. Taking the simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative TMA test within the first 4 weeks as predictors for treatment response, SVR rates were comparable between both treatment schedules with an SVR probability of >80% obtained in patients treated for only 18 or 24 weeks.
  
  
  CONCLUSIONS
  The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia.
authors: Universitätsklinikum Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany. thomas.berg@charite.de
authors: Thomas
authors: T
authors: Berg
authors: Viola
authors: V
authors: Weich
authors: Gerlinde
authors: G
authors: Teuber
authors: Hartwig
authors: H
authors: Klinker
authors: Bernd
authors: B
authors: Möller
authors: Jens
authors: J
authors: Rasenack
authors: Holger
authors: H
authors: Hinrichsen
authors: Tilman
authors: T
authors: Gerlach
authors: Ulrich
authors: U
authors: Spengler
authors: Peter
authors: P
authors: Buggisch
authors: Heike
authors: H
authors: Balk
authors: Myrga
authors: M
authors: Zankel
authors: Konrad
authors: K
authors: Neumann
authors: Christoph
authors: C
authors: Sarrazin
authors: Stefan
authors: S
authors: Zeuzem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D021121:Branched DNA Signal Amplification Assay; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a