Definition of rapid virologic response with a highly sensitive real-time PCR-based HCV RNA assay in peginterferon alfa-2a plus ribavirin response-guided therapy.
OBJECTIVE
Assessing hepatitis C virus (HCV)-RNA levels is integral to response-guided therapy. Rules for early discontinuation and determination of treatment duration were mainly established with HCV-RNA assays with a detection limit of 50IU/ml (COBAS Amplicor HCV [CA]). The currently used real-time PCR-based COBAS Ampliprep/COBAS-TaqMan HCV (CAP-CTM) test has a detection limit of approximately 10IU/ml. It is unknown whether shortening of treatment duration to 16/24 weeks in patients with rapid virological response at week 4 (RVR) and viral loads between 10 and 50IU/ml is possible.


METHODS
We reanalysed stored serum from two large, multinational, randomized trials in which patients were treated with peginterferon alfa-2a/ribavirin (n=962). Results of CAP-CTM with truly undetectable HCV RNA and those <15IU/ml, which includes patients with residual viraemia (<15), were compared with the originally obtained results using the CA assay.


RESULTS
RVR rates were comparable for CA (<50) and CAP-CTM (<15) with 32% and 32% for genotype (gt) 1 and 50% and 49% for gt2/3 patients, respectively. A significantly smaller number of samples really had truly undetectable HCV RNA by the CAP-CTM assay (24% for gt1, 37% for gt2/3). However, sustained virological response rates after shortened treatment (16/24weeks) were not significantly different in patients with a RVR <50, a RVR <15 and RVR undetectable (82%, 83%, 83% for 24weeks gt1 and 95%, 95%, 94% for 16weeks gt2/3).


CONCLUSIONS
Shortening the treatment duration to 16/24weeks can be performed on the basis of a RVR with HCV-RNA concentrations <15IU/ml by the CAP-CTM assay.
Sarrazin
Christoph
C
Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany. sarrazin@em.uni-frankfurt.de
Shiffman
Mitchell L
ML
Hadziyannis
Stephanos J
SJ
Lin
Amy
A
Colucci
Giuseppe
G
Ishida
Hiroshi
H
Zeuzem
Stefan
S
D000998:Antiviral Agents / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy / Q000821:virology
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