Last modified: 2014-06-09

#### Abstract

After the first approval of direct-acting antivirals, new targets are being developed and new treatment combinations are being developed. In order to describe this new treatment effects we have used a multiscale model that is able to describe a triphasic decline. This model combines approaches from two recently published multiscale models for HCV viral kinetics (1, 2). We started with an extended version of the standard model, the so called ICCI (Intracellular and Cellular Infection Model) (1). This model takes the intracellular replication cycle into account by introducing two new compartments inside the infected cells compartment. The first compartment describes the number of intracellular viral genomic units (positive genomic RNA strands, R) that are available for transcription and translation per infected cell and the second compartment describes the number of replication units (negative-strand/double-stranded RNA,R) that are available for synthesis of genomic RNA. During untreated chronic infection, R serves as a resource for the formation of replication units with rate beta while intracellular RNA strands will be produced by the replication units with rate alpha. During treatment, the total treatment effect is reflected by the relative reduction of the basic reproductive ratio given by (1-eps1)(1-eps2)/(1+k), where eps1 is the rate of blocking the viral production (0<=eps1<=1), eps2 is the rate of blocking the synthesis of intracellular RNA (0<=eps2<=1) and k=>0 is a parameter that potentially enhance the loss rate of intracellular RNA mimicking an approach for multiscale modeling by Guedj et al. (2). Our viral kinetic model is described by the differential equations system:

References

[1] Guedj, J. & Neumann, A. Understanding hepatitis C viral dynamics with direct-acting antiviral agents due to the interplay between intracellular replication and cellular infection dynamics Journal of theoretical biology, Elsevier, 2010, 267, 330-340

[2] Guedj, J.; Dahari, H.; Rong, L.; Sansone, N. D.; Nettles, R. E.; Cotler, S. J.; Layden, T. J.; Uprichard, S. L. & Perelson, A. S. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life Proceedings of the National Academy of Sciences, National Acad Sciences, 2013, 110, 3991-3996