An integrated modelling approach for R5-X4 mutation and HAART therapy assessment

Abstract

We have modelled the within-patient evolutionary process during HIV infection using different methodologies. During the HIV infection the arising of viral multi-strain of the virus able to use different coreceptors, in particular the CCR5 and CXCR4 (R5 and X4 phenotypes, respectively) influences the progression of the disease to the AIDS phase. We present a model of HIV early infection and CTLs response which describes the dynamics of R5 quasispecie and a model of HIV late infection, specifying the R5 and X4 switch and effect of immune response. We illustrate dynamics of HIV multiple strains on HAART and multidrug HAART therapy. The HAART combined with X4 strain blocker drug might help to reduce infectivity and that leads to slower progression of disease. On the methodology side, our model represents a paradigm of integrating formal methods and mathematical models as a general framework to study HIV multiple strains during disease progression, and will inch towards providing help in selecting among vaccines and drug therapies. The results here presented are one of the rare cases of methodological cross comparison (stochastic and deterministic) and the first implementation of model checking in therapy validation.