High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients is associated with increased peripheral CD8+ T cell counts. Hepatitis C virus (HCV) coinfection is an additional risk factor for the development of non-AIDS events. We found that, in HIV/HCV coinfection, the increased proportion of CD8+ T lymphocytes is due to the effector memory and terminal effector T cells gain. Moreover, in these patients, the accumulation of highly differentiated forms of CD8+ T lymphocytes was associated with increased concentrations of inflammatory indices.