The fragile relationship between hepatitis C virus and its human host.

Based on viral dynamics and replicative fidelity alone, suppression of hepatitis C virus (HCV) should be a substantially greater challenge than suppression of HIV. Factors underlying the greater than expected responsiveness of HCV to direct-acting antiviral (DAA) drugs include the vulnerability of HCV during acute infection, acceleration of second-phase viral decay kinetics with increased anti-HCV regimen potency, and the effect of DAA treatment in upsetting the equilibrium between the virus and the host immune system. Several potential mechanisms might explain the considerable vulnerability of HCV to potent antiviral therapy. It is possible that anti-HCV treatment destabilizes HCV replication complexes, thereby permitting cure of infected cells, and that with the rapid reduction of HCV within the hepatocyte, mechanisms by which HCV evades the innate and adaptive immune responses are undermined, thus enhancing the antiviral effect of potent anti-HCV regimens. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in New York, New York, in June 2013.