HIV infection is multi-faceted and a multi-step process. The virus-induced pathogenic mechanisms are manifold and mediated through a range of positive and negative feedback regulations of immune and physiological processes engaged in virus-host interactions. The fundamental questions towards understanding the pathogenesis of HIV infection are now shifting to 'dynamic' categories: (i) why is the HIV-immune response equilibrium finally disrupted? (ii) can one modify the dynamic equilibrium for host benefit? (iii) can one predict the outcome of a system perturbation via antiviral drugs or drugs modulating the host immune response dynamics? Answering these questions requires a major interdisciplinary effort, and in particular, the development of novel mathematical approaches for a coherent quantitative description and prediction of intra-patient HIV evolution, the immunological responses to HIV infection, and the systems level homeostatic regulation of specific effector and regulatory lymphocyte populations in correlation with disease status. Here we summarized fundamental biological features of HIV infection and current mathematical modelling attempts to understand HIV pathogenesis