title: Prediction of minimal residual viremia in HCV type 1 infected patients receiving interferon-based therapy.
abstract: BACKGROUND
  Complete suppression of viral replication is crucial in chronic HCV treatment in order to prevent relapse and resistance development. We wanted to find out which factors influence the period from being already HCV RNA negative by bDNA assay (< 615 IU/mL) to become undetectable by the more sensitive TMA test (< 5.3 IU/mL).
  
  
  METHODS
  Evaluated were 433 HCV type 1-infected patients. All of them received 1.5 ug/kg Peg-IFNα-2b plus ribavirin for 18-48 weeks. bDNA was performed weekly during the first 8 weeks and thereafter at weeks 12, 24, and 48. Patients who became bDNA undetectable were additionally analysed by TMA.
  
  
  RESULTS
  Of the 309 patients with on-treatment response (< 615 IU/mL), 289 also reached undetectable HCV RNA levels by TMA. Multivariate analysis revealed that viremia ≤ 400,000 IU/mL (p = 0.001), fast initial virologic decline (p = 0.004) and absence of fibrosis (p = 0.035) were independent predictors of an accelerated on-treatment response by TMA assay in already bDNA negative patients. bDNA negative patients becoming HCV RNA undetectable by TMA within the following 3 weeks had a frequency of relapse of 21%, whereas those showing TMA negativity after 3 weeks relapsed in 38% (p = 0.001). In RVR patients (bDNA < 615 IU/mL at week 4) the corresponding relapse rates were 15.3% vs. 37.5%, respectively (p = 0.003).
  
  
  CONCLUSIONS
  Early viral kinetics, baseline viremia and fibrosis stage are important tools to predict persistent minimal viremia during interferon-based therapy. The data have implications for designing a more refined treatment strategy in HCV infection, even in the setting of protease inhibitor-based triple treatment.
authors: Universitätsklinikum Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany.
authors: Viola
authors: V
authors: Knop
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: Konrad
authors: K
authors: Neumann
authors: Christoph
authors: C
authors: Sarrazin
authors: Stefan
authors: S
authors: Zeuzem
authors: Thomas
authors: T
authors: Berg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D005858:Germany; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014766:Viremia / Q000175:diagnosis / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b