Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively

Background: 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. Methods and Results: 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. Implications: 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.