5%) or tegobuvir/GS-9256/Peg-IFN/RBV arm (26.7%). Patients in all treatment arms had an initial sharp decline in plasma HCV RNA levels during the first 48 hours of therapy (Fig. 1). In the tegobuvir/GS-9256 arm, this decrease was generally maintained through day 7, after which HCV RNA levels began to rebound, associated with the emergence (i.e., detection) of resistance-associated variants. The addition of RBV to the treatment regimen increased the magnitude, extent, and duration of viral reduction; in the tegobuvir/GS-9256/RBV

arm, reductions in HCV RNA levels were observed through day 14 and were generally maintained through day 28. The addition of Peg-IFN alpha-2a had selleck chemical a similar additive effect; in the tegobuvir/GS-9256/Peg-IFN/RBV arm, reductions in HCV RNA levels were observed through day 28. The association of IL28B genotype

and initial antiviral response was variable, with a trend toward a greater magnitude of HCV RNA reductions in IL28B CC patients. No differences in mean maximal HCV RNA reduction by HCV subtype (i.e., 1a or 1b) were observed. Virologic responses in the 4 patients infected with other HCV-1 subtypes are presented in the Supporting Table. In each case, HCV RNA reductions from baseline during randomized therapy ranged from −0.75 to −2.84 log10 IU/mL. After the switch to Peg-IFN/RBV, RXDX-106 continued VL reductions were observed, ranging from −2.98 to −5.23 log10 IU/mL from baseline by week 6. In the primary efficacy analysis, a greater percentage of patients achieved RVR after receiving tegobuvir/GS-9256 in combination with RBV (38%), compared with tegobuvir/GS-9256 alone (7%) (Table 3). All patients (14 of 14) receiving tegobuvir/GS-9256 in combination with Peg-IFN/RBV achieved RVR. Excluding data points after the early introduction of Peg-IFN/RBV, the median

(i.e., Q1 and Q3) maximal reduction in HCV RNA was highest for patients receiving tegobuvir/GS-9256/Peg-IFN/RBV, −5.7 (−5.9, −5.5) log10 IU/mL, versus Fenbendazole −5.1 (−5.3, −4.4) for tegobuvir/GS-9256/RBV, and −4.1 (−4.4, −2.9) for tegobuvir/GS-9256 alone. Viral breakthrough was most common in the tegobuvir/GS-9256 arm, where the majority of patients (80%) started standard of care with Peg-IFN and RBV before day 28. Although RBV decreased and delayed breakthrough, in the tegobuvir/GS-9256/RBV arm, 31% started standard of care early because of the observed increases in HCV RNA at or before day 28. None of the patients receiving tegobuvir/GS-9256/Peg-IFN/RBV experienced viral plateau or rebound through day 28. For patients in the tegobuvir/GS-9256 arm who had an increase in HCV RNA levels observed at days 14 or 21, HCV RNA levels declined again by day 28 after initiating Peg-IFN and RBV. Among the patients who either did not experience early response or had viral rebound, several achieved RVR after starting either Peg-IFN or Peg-IFN and RBV early.