title: The Usefulness of Defining Rapid Virological Response by a Very Sensitive Assay (TMA) during Treatment of HCV Genotype 2/3 Infection.
abstract: The aim of this study was to determine in patients with HCV genotype 2 or 3 the performance at week 4 of two assays with different sensitivities for HCV RNA detection, for the prediction of SVR and stratification for treatment duration (14 and 24 weeks). Recruitment was from two trials comparing 14 and 24 weeks treatment to patients with rapid virological response (RVR) (n = 550). RVR was originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available frozen plasma sample drawn at week 4 and with follow-up data week 24 post-treatment were included (n = 429). HCV-RNA was prospectively measured with COBAS Amplicor V2, Roche (CA) (lower detection limit 50 IU/ml) and retrospectively assessed with VERSANT HCV-RNA Qualitative Assay, Siemens (TMA) (lower limit detection 10 IU/ml). Genotype 3 was present in 80% and genotype 2 in 20%. A SVR was achieved in 82%. At week 4 HCV-RNA was undetectable in 74.8% and 63% of serum samples tested with CA and TMA, respectively. CA undetectable/TMA positive was observed in 61/341 (18%) of the samples. In genotype 3 patients a relapse was seen in 9% of the patients with both CA and TMA undetectable and in 25% of the patients who were CA undetectable/TMA positive (p = 0.006). In patients allocated to 14 weeks treatment a relapse was observed in 11% of TMA undetectable patients and 26% of TMA positive (p = 0.031). In genotype 2 patients treated for 14 weeks relapse was observed in 6% of the patients with both CA and TMA undetectable week 4. Assays with high sensitivity for HCV RNA identifies patients at week 4 with high risk of virological relapse. We recommend that patients with genotype 3 and detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with pegIFN and ribavirin.
authors: Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Olav
authors: O
authors: Dalgard
authors: Institut National de la Santé et de la Recherche Médicale, U-773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris VII, Paris, France.
authors: Michelle
authors: M
authors: Martinot-Peignoux
authors: Medical Department, Malmø University Hopsital, Malmø, Sweden.
authors: Hans
authors: H
authors: Verbaan
authors: Clinic for specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Kristian
authors: K
authors: Bjøro
authors: Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Copenhagen, Denmark.
authors: Helmer
authors: H
authors: Ring-Larsen
authors: Service d'Hépatologie, Hŏpital Beaujon, Clichy, France.
authors: Patrick
authors: P
authors: Marcellin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects*; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage* / Q000494:pharmacology; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin