Abstract:
Systemic immune activation has emerged as an essential component of the immunopathogenesis of HIV. It not only leads to faster
disease progression, but also to accelerated decline of overall immune competence. HIV-associated immune activation is
characterized by an increase in proinflammatory mediators, dysfunctional T regulatory cells, and a pattern of T-cell-senescent
phenotypes similar to those seen in the elderly. These changes predispose HIV-infected persons to comorbid conditions that
have been linked to immunosenescence and inflamm-ageing, such as atherosclerosis and cardiovascular disease,
neurodegeneration, and cancer. In the antiretroviral treatment era, development of such non-AIDS-defining, age-related
comorbidities is a major cause of morbidity and mortality. Treatment strategies aimed at curtailing persistent immune
activation and inflammation may help prevent the development of these conditions. At present, the most effective strategy
appears to be early antiretroviral treatment initiation. No other treatment interventions have been found effective in large-scale
clinical trials, and no adjunctive treatment is currently recommended in international HIV treatment guidelines. This article
reviews the role of systemic immune activation in the immunopathogenesis of HIV infection, its causes and the clinical
implications linked to immunosenescence in adults, and the therapeutic interventions that have been investigated.
