Evolution and function of the HCV NS3 protease in patients with acute hepatitis C and HIV coinfection

- Prospective study of patients with acute hepatitis C and HIV coinfection.
- High HCV NS3 quasispecies diversity and complexity detected in acute hepatitis C.
- Longitudinally decreasing NS3 quasispecies evolution in spontaneous clearers.
- More pronounced viral load decline in patients with spontaneous clearance.
- CARDIF was cleaved to a similar extent independent of the outcome.

Little is known about the importance of the hepatitis C virus (HCV) NS3 protease in acute hepatitis C. In this prospective study, 82 consecutive patients with acute hepatitis C and human immunodeficiency virus (HIV) coinfection were enrolled. Individuals were infected with highly related HCV strains and the baseline NS3 quasispecies diversity and complexity was higher compared to a chronic hepatitis C control group (P<0.0001). Both parameters were comparable in patients with spontaneous clearance (n=6) versus treatment-induced SVR (n=5) or development of chronic hepatitis C (n=9). Longitudinal NS3 quasispecies kinetics showed a trend to a decreasing diversity and complexity (P<0.05) within 4 weeks in patients with spontaneous clearance compared to the other groups. The innate immune signalling protein CARDIF was cleaved to a similar extent independent of the outcome. Together with a more pronounced viral load decline (P<0.05), an early decreasing NS3 quasispecies evolution indicates spontaneous clearance of acute hepatitis C.