Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239

Abstract

: Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.

Figure 1

Change in Transaminase Levels during Pioglitazone Monotherapy; Median (Q1,Q3) Legend: Statistically significant declines in ALT and AST (expressed as absolute values (top boxes) and a ratio to the upper limit of normal (ULN) (bottom boxes)) occurred after the 24 week course of pioglitazone monotherapy. The statistical analysis was conducted using the ratio to ULN, since these were run at local labs with varying normal ranges [median (Q1,Q3) −0.14 (−0.47, 0.02) × ULN (p=0.031) and −0.20 (−0.29, −0.08) × ULN (p=0.018), respectively].