Alterations in high‐dimensional T‐cell profile and gene signature of immune aging in HIV‐infected older adults without viremia

Alterations in the components of the immune system occur with aging. The introduction of combination antiretroviral therapy (ART) has dramatically improved life expectancy in human immunodeficiency virus (HIV) infected individuals by suppressing viral replication and increasing CD4(+) T‐cell counts. Immunosenescence‐like changes, including the expansion of memory CD8(+) T cells with senescent features, are reported in young HIV‐infected individuals who do not have clinically detectable viremia on ART. However, it is less known whether HIV infection affects the immunosenescent status in older HIV‐infected individuals. Here, we addressed this question in older HIV‐infected, HIV‐uninfected, and frail individuals (all groups age ≥65 years) by examining a set of aging‐associated genes in peripheral blood mononuclear cells (PBMCs) as well as by analyzing subsets of CD4(+) and CD8(+) T cells in depth using high‐dimensional CyTOF analysis. Older HIV‐infected individuals had increased expression of aging‐associated genes such as CX3CR1 in PBMCs which are related to IL‐7 receptor low effector memory (IL‐7Rα(low) EM) CD8(+) T cells, a cell population known to expand with age. The subsets of IL‐7Rα(low) EM CD8(+) T cells expressing senescent, cytotoxic, and inflammatory molecules, including CD57, perforin, and CX3CR1, as well as memory CD4(+) T cells expressing CD161 and CXCR3, molecules associated with replication‐competent HIV‐1 harboring cells, were increased in older HIV‐infected individuals. Overall, older HIV‐infected individuals without detectable viremia on ART had augmented levels of age‐associated immune alterations in PBMCs, suggesting that HIV infection has a persistent impact on senescence in older HIV‐infected individuals despite the clinically controlled viremia.