title: Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy.
abstract: Interferon-free combination therapies lead to rapid suppression of HCV RNA early during treatment. The potential to predict virologic response and failure as well as to guide treatment duration with measurement of HCV RNA very early during treatment by highly sensitive assays is not well known. In 11 IL28B CC (rs12979860) patients infected with HCV genotype 1, who received DAA combination therapy with the NS3 protease inhibitor ABT-450/r together with the non-nucleoside NS5B polymerase inhibitor ABT-072 and ribavirin for 12 weeks, HCV RNA was assessed frequently by the RealTime HCV (ART) and the High-Pure-System/Cobas TaqMan (HPS) assays during and after treatment. Overall, at 33 of 131 time points during treatment residual HCV RNA was detectable by ART but undetectable by HPS while the converse was observed in only two samples. Of the two patients who experienced virologic relapse, one patient had residual viremia at week 6 of treatment by ART only while the other patient never had undetectable HCV RNA by the ART assay. However, residual viremia was also observed by ART as late as therapy weeks 9, 10 and 12 in patients with subsequent sustained virologic response. In patients with sustained response no viremia was observed at multiple time points during post-treatment follow up by either assay. The higher sensitivity of the ART in comparison to the HPS assay may be associated with more frequent detection of residual viremia during highly effective, interferon-free combination therapies. However, the significance of this finding in predicting virologic failure appears to be limited.
authors.affiliation: Goethe University Hospital, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Abbott Molecular, Des Plaines, IL, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cloherty
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Cohen
authors.affiliation: Henri Mondor Hospital, Créteil, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Chevaliez
authors.affiliation: Abbott Molecular, Des Plaines, IL, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Herman
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
authors.affiliation: Henri Mondor Hospital, Créteil, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000627:therapeutic use*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination / Q000379:methods; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D010865:Pilot Projects; D011379:Prognosis; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use; D013449:Sulfonamides; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D012367:RNA, Viral; D013449:Sulfonamides; D012254:Ribavirin; D011392:Proline; C585405:paritaprevir
keywords: Clinical trials; Direct acting antiviral; Hepatitis C; Vial load