[63] Two phase 2a trials (PILOT and

COPILOT) investigated another potent viral protease AZD2281 nmr inhibitor, ABT-450, boosted with low-dose ritonavir in combination with RBV and a non-nucleoside inhibitor of RNA polymerase (ABT-072 or ABT-333).[37, 64] Both trials demonstrated SVR rates above 90% in treatment-naïve patients, whereas 47% of treatment-experienced patients achieved SVR.[37, 64] A larger phase 2b trial (AVIATOR) added ABT-267 (an NS5A inhibitor) and demonstrated SVR12 rates of 99% in treatment-naïve patients and 93% in previous null responders with 12 weeks of therapy.[36] In the PEARL-1 trial, patients with genotype 1b infection received ABT-450/r and ABT-267. SVR12 was achieved by 95%

of treatment-naïve patients and 90% of prior null responders.[65] A large number of phase 3 trials are now underway testing various DAAs and DAA combinations for treatment of chronic HCV. In general, these trials are designed without RGT. If the results of phase 2 trials are confirmed, treatment of HCV could become much more effective and much simpler in the near future, leading to eradication of infection in > 90% of patients without the use of RGT. RGT for the treatment of genotype 1 HCV infection NSC 683864 datasheet is the current standard of care for IFN-based therapy with telaprevir or boceprevir, and has undoubtedly spared countless patients from unnecessarily long treatment durations, as well as the side-effects and costs associated with PegIFN/RBV therapy. Despite these benefits, the need to monitor HCV RNA levels during treatment adds another layer of complexity to already complex treatment regimens. The increased potency of DAAs is allowing more rapid viral kinetics in both the first and second phases of viral load declines, reducing the need for on-treatment measurements of response for determining duration of therapy. These improvements will likely lead to

the approval of IFN-free regimens in the near future. All-oral direct antiviral therapies are expected to have high cure rates with short treatment duration and limited adverse events. Furthermore, treatment regimens will likely be simpler, without requiring on-treatment measurement of response, and likely 上海皓元医药股份有限公司 not requiring pretreatment assessment of factors that have traditionally influenced response rates—such as HCV genotype, IL28B genotype, baseline viral load, and degree of fibrosis. In the future, studies will focus on the improvement of SVR rates in special populations of patients with HCV including those with compensated and decompensated cirrhosis, prior null response (particularly those with genotype 3 infection), renal failure, and HCV recurrence after a liver transplant. The role of RGT in these groups is still to be determined.