BACKGROUND: Despite effective antiretroviral therapy (ART), HIV-infected patients exhibit systemic inflammation, early onset of age-related diseases, and features of immunosenescence. The role of inflammation in the development of age-related diseases is widely recognized. However, the role of immunosenescence is not well established. Studying immunosenescence in HIV-infection could give insight into its role in ageing processes. In this cross-sectional study, we aimed to investigate whether ART-treated HIV-infected patients exhibit immunosenescence; and whether immunosenescence is associated with age-related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA; senescence: killer cell lectin-like receptor G1 (KLRG1); and exhaustion: programmed death-1 (PD-1). Relationships between CD8 (+) T cell immunosenescence, exhaustion, and age-related processes were assessed using linear regressions.
RESULTS: HIV-infection was strongly associated with more highly differentiated and mature CD8 (+) T cell phenotypes. PD-1 and KLRG1 expression did not differ between HIV(+) and Controls, but depended on differentiation and maturation stages of the cells. CD8 (+) T cell maturation was associated with age. KLRG1 expression was associated with age, metabolic syndrome, visceral adipose tissue, and high muscle mass. PD-1 expression was not associated with age-related parameters.
CONCLUSIONS: HIV-infection strongly affected CD8 (+) T cell differentiation and maturation, whereas age-related processes were only weakly associated with immune parameters. Our findings suggest that, in contrast to inflammation, immunosenescence appears to be highly dependent on HIV-infection and is only to a small extent associated with age-related parameters in well-treated HIV-infection.