Viral Kinetics OR What happens when you start treatment
- 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
: J Hepatol 1999;31 Suppl 1:61-4
Clinical implications of hepatitis C viral kinetics.
Medizinische Klinik II, Klinikum der Johann Wolfgang
Frankfurt a.M., Germany. Zeuzem@...-frankfurt.de
Antiviral treatment of patients with chronic hepatitis C can perturb
steady-state of virus production and clearance. From serial
changes in viremia, kinetic information on the dynamics of hepatitis C
(HCV) replication can be obtained. After a delay of about 9 h due to
interferon-a pharmacokinetics, the decline of viremia in patients
with interferon-alpha is characterized by a concave shape. In the first
(day 1) a rapid dose-dependent decline in viral load is observed. The
phase viral decline (> or =day 2) shows a much slower decline with no
pronounced differences between the applied interferon-alpha schedules.
a first phase decline can be observed in almost all patients treated
interferon-alpha, non-responders typically reveal no further decline of
viremia during the second phase. Kinetic analysis showed that
therapy with interferon-alpha plus ribavirin has no direct synergistic
antiviral effect in the initial 4 weeks of treatment of HCV-infected
with 6 MU IFNalpha three times per week. Calculations revealed a
virus production and clearance per day in patients with chronic
of approximately 10(10)-10(12) virions per day and an in vivo half-life
the virus in the order of a few hours. The high turnover rates of HCV
the rapid generation of viral diversity and the opportunity for viral
from the host immune surveillance and antiviral therapy. The
derived from HCV kinetics comprise the consideration of more aggressive
initial dosing regimens (especially daily doses), the possibility to
therapy individually not only according to pretreatment parameters but
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.
PMID: 10622562, UI: 20086274
Hepatitis C virus: kinetics and quasispecies evolution during anti-viral
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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