HCV-specific T-cell response in relation to viral kinetics and treatment outcome (DITTO-HCV project).
OBJECTIVE
The second slope of viral decline induced by interferon treatment has been suggested to be influenced mainly by the hepatitis C virus (HCV)-specific T-cell response; however, this hypothesis needs to be validated by results derived from experimental studies.


METHODS
To address this issue, the HCV-specific T-cell response of 32 genotype-1-infected patients of the 270 patients enrolled in the dynamically individualized treatment of hepatitis C infection and correlates of viral/host dynamics phase III, open-label, randomized, multicenter trial was studied in relation to viral kinetics and treatment outcome.


RESULTS
Greater proliferative responses by HCV-specific CD8 cells were found before treatment in patients with a fast viral decline and with a sustained viral response. However, no significant improvement of HCV-specific CD8 responses was observed in the first weeks of therapy in both rapid viral responder and non-rapid viral responder patients. A mild enhancement of proliferative T-cell responses and a partial restoration of the cytotoxic T-cell potential was expressed only late during treatment, likely favored by HCV clearance.


CONCLUSIONS
Early restoration of an efficient T-cell response does not seem to be an essential requirement for a rapid viral decline in the first weeks of treatment. However, patients presenting a better HCV-specific CD8 cell proliferative potential at baseline are more likely to present a rapid and sustained viral response. Therefore, future treatment protocols should consider the development of strategies aimed at improving HCV-specific T-cell responses.
Pilli
Massimo
M
Azienda Ospedaliero-Universitaria Di Parma, Parma, Italy.
Zerbini
Alessandro
A
Penna
Amalia
A
Orlandini
Alessandra
A
Lukasiewicz
Esther
E
Pawlotsky
Jean-Michel
JM
Zeuzem
Stefan
S
Schalm
Solko W
SW
von Wagner
Michael
M
Germanidis
Georgios
G
Lurie
Yoav
Y
Esteban
Juan I
JI
Haagmans
Bart L
BL
Hezode
Christophe
C
Lagging
Martin
M
Negro
Francesco
F
Homburger
Yonit
Y
Neumann
Avidan U
AU
Ferrari
Carlo
C
Missale
Gabriele
G
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D018963:Hepatitis Antigens / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D018963:Hepatitis Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a