There are limited data evaluating the influence of HCV protease inhibitors, nucleotides and other direct acting antiviral (DAAs) drug classes on the metabolic milieu of HCV treatment recipients. In one study of HCV mono-infected study participants receiving 14 days of monotherapy with the protease inhibitor danoprevir, serum HCV RNA and HOMA-IR [Appendix I] correlated significantly (Spearman rho=0.379, p<0.0001).17 At baseline, mean serum HCV-RNA level and mean HOMA-IR score were 6.2±0.5 log10 IU/ml and 3.8±1.9, respectively. At the end of 14 days of Danoprevir monotherapy the mean decrease in HCV RNA was 2.2±1.3 log10 IU/ml (p<0.0001) in patients who received the active drug (n=40). Concurrent with this, the mean HOMA-IR score decreased by 1.6±1.1 (p<0.0001), with a close correlation between HOMA-IR improvement and viral load decline. In contrast, HCV-RNA and HOMA-IR remained unchanged in placebo recipients. The effect of HCV-protease inhibitors and other DAAs on glucose metabolism beyond 14 days of treatment has not been established.