HCV genotype 1 and 4 are the most frequent among the non-responding patients, who reveal similar characteristics when compared to genotype 2 and 3. This could explain why these two first groups appear so scarcely reacting to the therapy.
Not only half of the patients’ population does not respond effectively to the present HCV therapies, the half that does respond, still suffers from severe side effects, which often lead to a discontinuation of the therapy. It has become clear that, if not reacting at the first treatment with peg-interferon and Ribavirin, existing long-term therapies are not able to reduce the disease progression in patients with chronic HCV and advanced fibrosis, with or without cirrhosis.
The classic combination approach is compromised by a variety of side effects, for example, anaemia. A solution to the anaemia problem would be reducing the Ribavirin doses, but this will result in a loss of efficacy. Usually, patients who do not respond to a first therapy cycle of combined interferon and Ribavirin, rarely show a positive reaction to a second one. Meanwhile, preclinical studies have evidenced that HCV viruses may quickly create resistance to the more recent class of protease inhibitors.
This means that it will be necessary to combine drugs with different active principles and resistance profiles. In short, we need to develop new pharmaceutical strategies.