Memory T-cell proliferation before HCV therapy predicts antiviral immune responses and treatment success

The contribution of the host immune system to efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal, prospective study of 33 individuals with chronic HCV treated with combination PEG-interferon-ɑ, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine if kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T-cell proliferation before therapy both predicted SVR and was associated with the magnitude of HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor, T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict both SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.