Chronic inflammation and immune activation occur in both HIV infection and normal aging and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear.

We measured established innate immune aging biomarkers in 309 individuals including 88 virologically suppressed (VS) and 52 viremic (viral load ≤ and >50 copies per milliliter, respectively) HIV-positive individuals. Levels of soluble (ie, CXCL10, soluble CD163, neopterin) and cellular (ie, proportions of inflammatory CD16 monocytes) biomarkers of monocyte activation were increased in HIV-positive individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV-positive individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older, respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg, neopterin) with age, whereas in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified CXCL10 as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker.

These findings may partially explain the increased prevalence of inflammatory age-related diseases in HIV-positive individuals and potentially indicate the pathological mechanisms underlying these diseases, which persist despite viral suppression.