1Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
2Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
3The Kirby Institute, UNSW Sydney, Sydney, Australia.
4Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada.
5Department of Immunology, University of Toronto, Toronto, ON, Canada.
6Department of Medicine, University Health Network, Toronto, ON, Canada.
7Departments of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
8Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment-induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct-acting antivirals (DAA) prevents establishment of, or reverses, T cell exhaustion, leading to a virus-specific T cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV-specific T cell responses before and after DAA or interferon-based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme-linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n=17), acute interferon (n=14), acute DAA (n=13) and chronic DAA (n=11). After controlling for sex, the magnitude of post-treatment HCV-specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV-specific responses post-treatment. However, individuals with spontaneous clearance had broader HCV-specific responses.