Hepatitis C viral kinetics in plasma and peripheral blood mononuclear cells during pegylated interferon-alpha2a/ribavirin therapy.
OBJECTIVE
Analysis of hepatitis C virus (HCV) RNA kinetics in compartments other than plasma may help in understanding HCV replication and identifying clinically significant patterns of treatment response.


METHODS
After 6 weeks of pegylated interferon-alpha2a/ribavirin therapy, 74 chronic hepatitis C patients were randomized to individualized or standard treatments for another 42 weeks. HCV RNA was quantified in peripheral blood mononuclear cells (PBMCs) by TaqMan-based real-time PCR and compared to plasma HCV RNA.


RESULTS
HCV RNA declines in PBMCs and plasma were comparable during the initial 12 weeks of therapy (Spearman's rank correlation range over different time points, 0.73-0.97). However, a delay of HCV RNA decay in PBMCs, expected if kinetics in PBMCs only reflected kinetics in plasma, was rarely observed. For many patients, HCV RNA decline in PBMCs started as early as in plasma and for some of them the kinetics strongly differed in the two compartments, hinting at a compartment-specific HCV replication and treatment effect. Fast viral decay in PBMCs was associated with sustained virological response, but viral kinetics in PBMCs added only minor predictive information compared with kinetics in plasma.


CONCLUSIONS
Future kinetics studies of HCV RNA during therapy with new antivirals should take into account their compartment-specific effect.
Pugnale
Paolo
P
Department of Pathology and Immunology, University of Geneva Medical Center, 1211 Geneva, Switzerland.
Herrmann
Eva
E
Neumann
Avidan U
AU
Pawlotsky
Jean-Michel
JM
Schalm
Solko W
SW
Ferrari
Carlo
C
Homburger
Yonit
Y
Zeuzem
Stefan
S
Negro
Francesco
F
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin