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Modelling hepatitis C virus kinetics: the relationship between the infected cell loss rate and the final slope of viral decay.

Abstract

Patients infected with hepatitis C virus (HCV) who respond to treatment with interferon-alpha plus ribavirin exhibit biphasic or triphasic viral load decreases. While the rapid first phase is indicative of the effectiveness of therapy in blocking viral production (epsilon), the slope of the final phase (lambda), that is, the second phase in biphasic decreases and the third phase in triphasic decreases, depends on the infected cell loss rate (delta). In standard models, lambda is approximately epsilondelta when the viral clearance rate c>delta, as has been previously estimated.

Our results indicated that in patients undergoing therapy who achieved a 2 log(10) reduction in viral load (epsilon99% should allow for a more accurate estimate of delta in HCV RNA kinetic studies. This might be important when using viral kinetics to estimate the effect of the immune response on viral elimination and the attainment of sustained virological response.

The relationship among epsilon, delta, lambda and the baseline fraction of HCV-infected hepatocytes (pi) was investigated in a model that included proliferation of hepatocytes.

We found that lambda was not proportional to epsilon, but rather obeyed a complex relationship that could lead to dramatic increases in estimates of delta as epsilon increased. In particular, when epsilon99%, delta approximately lambda regardless of pi.

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Citation:

Dahari H, Shudo E, Cotler SJ, Layden TJ, Perelson AS. (2009). Modelling hepatitis C virus kinetics: the relationship between the infected cell loss rate and the final slope of viral decay. Antiviral therapy, 14(3)