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  • Title: The effect of controlled therapy interruption in chronic HCV infection: enhanced host immune response? A hypothesis.
    Author: Lake-Bakaar G.
    Journal: J Clin Virol; 2009 Feb; 44(2):149-51. PubMed ID: 19157972.
    Abstract:
    BACKGROUND: We have hypothesized that prolonged viral suppression partially reverses immune tolerance in chronic hepatitis C virus infection. Brief periods of treatment interruption can then simulate 'auto-vaccination' and evoke powerful secondary host immune responses. OBJECTIVE: To determine the effect of controlled therapy interruption CTI on viral load in previous relapsers to interferon and ribavirin treatment. STUDY DESIGN: Virus is maintained at undetectable levels for 2-8 weeks with pegylated interferon and ribavirin and then briefly interrupted, restarting as soon as viremia returns (cycle 1). It is suppressed for at least a further 4 weeks, then briefly interrupted again (cycle 2). RESULTS: Viremia relapsed within 2-4 weeks (time to relapse TTR) after the first treatment interruption in all four patients in cycle 1. TTR increased sevenfold with the second treatment interruption in patient 1 and was followed by sustained virological response with cycle 3. In patient 2, TTR increased threefold after cycle 2 and subsequent cycles. Serum ALT and bilirubin rose significantly with treatment interruption during cycles 2 and 3, returning to baseline with treatment resumption. Serum bilirubin rose to 12.3mg/dl when two doses of pegylated interferon were missed during cycle 4. In patients 3 and 4, TTR was unchanged after three consecutive cycles. However, VL has remained more than 1 log below baseline for up to 18 months in both. CONCLUSIONS: These observations suggest that CTI exerts significant control of chronic hepatitis C viremia.
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