Changes in T-cell subsets in HIV-HCV-coinfected patients during pegylated interferon-alpha2a plus ribavirin treatment.
BACKGROUND
We evaluated the effect of different doses of pegylated interferon (PEG-IFN)-alpha2a/ribavirin (RBV) on several T-cell activation markers in HIV-HCV-coinfected patients and their relationship with changes in plasma HCV RNA.


METHODS
Frozen peripheral blood mononuclear cells (PBMCs) from 22 patients receiving two different PEG-IFN-alpha2a schedules were analysed by six-colour flow cytometry. Cell-surface expression of CD38 was quantified. HIV and HCV viral loads, as well as absolute CD4+ and CD8+ T-cell counts, were recorded during the follow up (72 weeks).


RESULTS
PEG-IFN-alpha2a/RBV treatment decreased the absolute numbers of CD8+ and CD4+ T-cells. The decrease in CD8+ T-cells was more pronounced, resulting in increased percentages of CD4+ T-cells. Percentages of naive/memory CD4+ T-cell subsets remained unchanged, although the percentage of CD38+CD45RO+ cells significantly increased. By contrast, the CD8+ T-cell compartment significantly reduced the percentage of CD45RO+ cells and HLA-DR+ cells, whereas the percentage of CD38 expressing cells was increased because of a significant increase in cell-surface CD38 expression. Changes in CD8+ T-cells were similar for both PEG-IFN-alpha2a/RBV doses, but high doses induced more severe perturbations in CD4+ T-cells. All changes returned to baseline levels after treatment cessation and, except for the loss of naive CD4+ T-cells, were not associated with virological response.


CONCLUSIONS
Transient lymphopaenia induced by PEG-IFN-alpha2a/RBV differentially affects T-cell subsets. Activated HLA-DR+ and CD45RO+ cells were selectively reduced in peripheral blood, whereas CD38 expression was up-regulated mainly in memory cells. Increasing PEG-IFN-alpha2a/RBV doses mainly affect CD4+ T-cells but failed to modify clinical outcome.
Fundació irsiCaixa-HIVACAT, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, Hospital Germans Trias, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
Marta
M
Massanella
Cristina
C
Tural
Laura
L
Papagno
Elisabet
E
Garcia
Antoni
A
Jou
Margarita
M
Bofill
Brigitte
B
Autran
Bonaventura
B
Clotet
Julià
J
Blanco
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D051997:ADP-ribosyl Cyclase 1; C100416:peginterferon alfa-2a