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Viral Kinetics OR What happens when you start treatment

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  • Claudine Crews
    Did you ever wonder what exactly is happening when you take that first injection of interferon? If so, here are 2 articles on viral kinetics, and
    Message 1 of 1 , May 1, 2000
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      Did you ever wonder what exactly is happening when you take that first
      injection of interferon? If so, here are 2 articles on viral kinetics, and
      implications.



      : J Hepatol 1999;31 Suppl 1:61-4


      Clinical implications of hepatitis C viral kinetics.

      Zeuzem S

      Medizinische Klinik II, Klinikum der Johann Wolfgang
      Goethe-Universitat,
      Frankfurt a.M., Germany. Zeuzem@...-frankfurt.de

      Antiviral treatment of patients with chronic hepatitis C can perturb
      the
      steady-state of virus production and clearance. From serial
      measurements of
      changes in viremia, kinetic information on the dynamics of hepatitis C
      virus
      (HCV) replication can be obtained. After a delay of about 9 h due to
      interferon-a pharmacokinetics, the decline of viremia in patients
      treated
      with interferon-alpha is characterized by a concave shape. In the first
      phase
      (day 1) a rapid dose-dependent decline in viral load is observed. The
      second
      phase viral decline (> or =day 2) shows a much slower decline with no
      or less
      pronounced differences between the applied interferon-alpha schedules.
      While
      a first phase decline can be observed in almost all patients treated
      with
      interferon-alpha, non-responders typically reveal no further decline of
      viremia during the second phase. Kinetic analysis showed that
      combination
      therapy with interferon-alpha plus ribavirin has no direct synergistic
      antiviral effect in the initial 4 weeks of treatment of HCV-infected
      patients
      with 6 MU IFNalpha three times per week. Calculations revealed a
      minimum
      virus production and clearance per day in patients with chronic
      hepatitis C
      of approximately 10(10)-10(12) virions per day and an in vivo half-life
      of
      the virus in the order of a few hours. The high turnover rates of HCV
      explain
      the rapid generation of viral diversity and the opportunity for viral
      escape
      from the host immune surveillance and antiviral therapy. The
      implications
      derived from HCV kinetics comprise the consideration of more aggressive
      initial dosing regimens (especially daily doses), the possibility to
      optimize
      therapy individually not only according to pretreatment parameters but
      also
      according to the initial decline of viral load and the perception that
      eradication of the virus will rely on the half-life of infected cells.

      Publication Types:
      Review
      Review, tutorial

      PMID: 10622562, UI: 20086274

      ********************************************

      Hepatitis C virus: kinetics and quasispecies evolution during anti-viral
      therapy.

      Forum (Genova) 2000 Jan-Mar;10(1):32-42 (ISSN: 1121-8142)

      Zeuzem S [Find other articles with this Author]
      Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universit t,
      Frankfurt am Main, Germany.

      The balance of virus production and clearance for untreated patients with
      chronic hepatitis C changes into a decline of viraemia when initiating
      effective anti-viral treatment. During the first phase of interferon-alpha
      (IFN-a) therapy, the kinetics of the viral load is characterised by a rapid
      dose-dependent decline starting after a delay of about eight to nine hours.
      This early response can be observed for almost all patients treated with
      IFN-a. After about 24 to 48 hours, the viral decline slows down leading to a
      second phase with a relatively stable exponential decay. Some non-responding
      patients show a nearly constant viraemia and some even a rebound throughout
      this second phase. Kinetic models allow the estimation of rates of viral
      production and clearance and reveal high turnover rates of hepatitis C virus
      (HCV) and an in vivo half-life of hepatitis C virions of a few hours, only.
      Due to the continuous and high replication rate in vivo, the low fidelity of
      the ribonucleic acid (RNA)-dependent RNA polymerase, and the immune
      surveillance of the host, HCV exists in an individual patient as a
      heterogeneous population of related viruses (quasispecies). A high degree of
      quasispecies variability correlates with a lower response to IFN-a therapy.
      Changes of the quasispecies population are more pronounced after initiation
      of treatment with IFN-a or interleukin-12 than during the natural course of
      disease. Ribavirin, however, has not been found to affect the HCV
      quasispecies population. Identification of a specific region within an
      envelope-encoding gene as the most variable region of HCV and as a critical
      neutralisation domain suggests that viral escape mechanisms are a possible
      cause for chronification and poses a major challenge for the development of
      a broadly reactive vaccine against HCV.

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