HIV infection as a model of accelerated immunosenescence

Abstract

Since its discovery in 1983, HIV-1 has become the most extensively studied pathogen in history. Massive CD4+ T-cell depletion and sustained immune activation and inflammation are hallmarks of HIV-1 infection. However, the precise pathway to the onset of immunodeficiency that develops during HIV-1 infection has not been resolved yet. In recent years, an intriguing parallel between HIV-1 infection and ageing has emerged: HIV-1 infected individuals present immunological alterations that are remarkably similar to those accumulated with age by HIV-1 uninfected elderly. These alterations, e.g., loss of regenerative capacity and accumulation of ageing T-cells, are suggestive of a process of immunosenescence, which may result from persistent HIV-1 replication and systemic immune activation. Furthermore, the comparison between HIV-1 infection and human ageing may go beyond the sole onset of immunosenescence, and extends to the deterioration of a number of physiological functions related to inflammation and systemic ageing. In the present chapter, we provide to the readers the different pieces of the HIV pathogenesis puzzle, from the virus itself to the development of therapeutic strategies, and discuss how they fit together into a model of accelerated immunosenescence and systemic ageing in HIV infection.