We first evaluated the evolution of naïve T-cell subsets in three groups of HCV infected individuals: 1) Acute HCV infection (n = 8), defined as ,6 months post estimated date of infection; 2) chronic HCV infection (n = 8), defined as .6 months post estimated date of infection; and 3) HIV/HCV co-infected individuals (n = 10). In all groups, patients were enrolled at the beginning of IFNa therapy and were followed for a total of 4 months. While, for any group of patient's, naïve CD4+ and CD8+ T-cell counts were not significantly different from healthy individuals (figure 1A), as early as one month following treatment initiation, naïve CD4+ T-cell counts were significantly reduced in chronically HCV-infected patients (39%, 58%, 46% and 35% decrease at M1, M2, M3 and M4 respectively; p#0.025; Figure 1B , top central panel). A similar trend was also observed in the CD8 compartment (40%, 39%, 33% and 33% decrease; Figure 1B , bottom central panel). A comparable effect was also observed in most co-infected patients (mean cell count declines were 19%, 32%, 52% and 43% at M1, M2, M3 and M4 in the CD4+ T-cell compartment and 9%, 21%, 41% and 42% in CD8+ T-cell subset; p#0.05 by M2-M3; Figure 1B , right panels). In contrast, naïve T-cell counts were only barely affected in acutely-HCV infected patients under IFNa therapy ( Figure 1B , left panels). Similarly, central memory CD4+ T-cells (CD45 RA-CCR7+; TCM) demonstrated 38% and 28% decrease in HCV and HIV/HCV patients respectively (59% and 60% in CD8+ TCM) while effector memory (CD45RA2 CCR7-; TEM) CD4+ T-cell counts declined by 45% and 10% in the same groups (61% and 65% in CD8+ TEM) ( Figure S1 ).