Aging of the human innate immune system in HIV infection

• A dysregulated pro-inflammatory state is present in both aging and HIV infection.
• Age- and HIV-related changes in TLR function may contribute to this dysregulation.
• DNA DAMPs, other viruses, fat and hormonal changes also result in dysregulation.
• Effects of microbial translocation and antiretroviral drugs may accumulate with age.
• HIV disease, therapy duration and comorbid illnesses complicate studies of aging.

HIV infection is associated with a chronic inflammatory state arising from multiple factors, including innate immune recognition of HIV, increased microbial translocation, and release of endogenous ligands from damaged cells (such as CD4 T cells). In many respects, this heightened pro-inflammatory environment resembles that associated with aging in the absence of HIV infection, and evidence of dysregulated innate immune responses can be found in not only older HIV-negative adults, but also adults with HIV infection. While the study of innate immune aging in HIV infection is still in its early stages, it seems likely that at least additive, or potentially synergistic effects of aging and HIV infection will be found.