Low-level HCV viraemia after initial response during antiviral therapy: transcription-mediated amplification predicts treatment failure.
BACKGROUND
In chronic hepatitis C patients with an initial virological response (IVR) during antiviral therapy (that is, HCV RNA becomes negative before week 16 of treatment) the significance of reappearing viraemia below the detection limit of PCR is not known. We studied this phenomenon in subsets of patients.


METHODS
We assessed HCV RNA at weeks 16 and 20 of therapy by PCR and by more sensitive transcription-mediated amplification (TMA) in 23 patients with breakthrough or relapse and in 34 patients with sustained virological response (SVR). All patients participated in a high-dose-interferon induction study for difficult-to-treat patients. Therapy consisted of amantadine hydrochloride and ribavirin, combined with interferon-alpha2b induction during the first 6 weeks and thereafter combined with weekly pegylated interferon-alpha2b.


RESULTS
Among the 57 IVR patients, we detected transient or persistent reappearance of low levels of HCV RNA in 10 of the 23 (43%) patients with eventual breakthrough or relapse; but in none of the 34 SVR patients. In 5 of 10 patients reappearing HCV RNA was only detectable by TMA.


CONCLUSIONS
Reappearance of low levels of HCV RNA in patients with IVR predicts treatment failure.
Gelderblom
Huub C
HC
Section of Clinical Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. h.c.gelderblom@amc.uva.nl
Reesink
Henk W
HW
Beld
Marcel G H M
MG
Weegink
Christine J
CJ
Jansen
Peter L M
PL
Dijkgraaf
Marcel G W
MG
Zaaijer
Hans L
HL
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D012680:Sensitivity and Specificity; D013045:Species Specificity; D017211:Treatment Failure; D014766:Viremia / Q000175:diagnosis
D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral