The Era of Direct-acting Antivirals Has Begun

The Beginning of the End for HCV?

Marie-Louise Vachon, M.D., M.Sc.; Douglas T. Dieterich, M.D.


Semin Liver Dis. 2011;31(4):399-409. 

In This Article


One of the most important results, if not the most important, in the study of DAAs in the year 2011 was the result of the phase IIa study evaluating quadruple therapy with the PI BMS-650032 (600 mg twice daily) and BMS-790052 (an HCV NS5A replication complex inhibitor; 60 mg once daily) with and without pegIFN/RBV for 24 weeks in patients with HCV genotype 1 who were prior null responders to IFN-based therapy.[26] Prior null responders are typically the most difficult-to-retreat patient population. In this study four (36%) of the 11 null responders who received BMS-650032 and BMS-790052 alone for 24 weeks achieved SVR. This result is proof of the concept that HCV can be cured without pegIFN/RBV. Of the 11 patients in this arm, six had a viral breakthrough and resistant variants to both drugs were detected.[27] In four of these six, HCV RNA became undetectable when pegIFN/RBV was added at the time of viral breakthrough. All 10 patients who received the quadruple therapy were cured. There was 100% SVR12 and 90% SVR24 (one patient had SVR12, detectable HCV RNA 6 months posttreatment and undetectable HCV RNA when retested later on). These two DAAs are currently being evaluated in a phase IIb study in combination with pegIFN lambda (BMS-914143) with and without ribavirin for 24 weeks in patients with chronic HCV genotype 1 naïve to treatment. This study also compares the use of a single DAA (either BMS-650032 or BMS-790052) with RBV and either pegIFN-lambda or pegIFN-alfa. It will be very interesting to learn the role of RBV when these two DAAs are combined with pegIFN.


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