Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response

The introduction of direct-acting antiviral (DAA) therapy has been a game-changer in the elimination of hepatitis C virus infection. DAAs treatment achieved higher rates of sustained virological response among HCV-infected individuals across different virus genotypes. DAAs directly target HCV viral several proteins in the HCV lifecycle resulting in controlling the infection. So far, the immune system also plays a crucial role in effective viral eradication. Prolonged antigen exposure, coupled with high viral loads, are key factors that drive immune system failure and the development of chronic infection. T cell exhaustion is the hallmark of the failure of immune response to eliminate the infection. Several sequelae contribute to T cell exhaustion, including the failure of CD8+ and CD4+ T cells, the expansion of the immune suppressive effects of regulatory T cells, and the modulation of epigenetics, which collectively contribute to the persistence of HCV infection. The interplay between DAA therapy and the influence on immune response particularly T cell exhaustion is still an opening question. In this review, we shed light on the recent studies exploring the impact of DAA therapy on CD8+ and CD4+ T cell response as well as the epigenetics change. We also aim to bridge the gap in the new approaches to HCV control.