Frontiers in Immunology · Oct 30, 2026
Inflammatory Biomarkers and Clinical Domains of Ageing in Older Adults with HIV
By Matilde Sánchez-Conde, María Jose Galindo, Isabel Machuca et al.
Background: Older adults with HIV (OAWH) experience frailty and functional impairment despite optimal ART. Markers of persistent inflammation and immune activation have been linked to ageing-related outcomes in people with HIV, but their relationships with clinically relevant ageing-related domains remain incompletely characterised. We examined associations between inflammatory and immune-activation biomarkers and ageing-related clinical domains in a cohort of OAWH. Methods: Subanalysis of the multicentre FUNCFRAIL cohort (NCT03558438). We measured circulating markers of inflammation and immune activation (sCD14, sCD163, FABP2/I-FABP, VCAM-1, hsCRP and IL-6), and, in a subset of participants, global DNA methylation in peripheral blood mononuclear cells. Frailty, physical performance and nutritional risk were assessed. Associations were analysed using correlation, Receiver Operating Characteristic (ROC) curves and multivariable regression. Results: Participants were 23% women, with a median age 56 years, with long-standing HIV infection (median 21 years); 48% had ≥3 comorbidities and 8% were frail. In multivariable analyses, greater walking speed was independently associated with lower IL-6 levels (B=-0.531; p<0.01), while longer duration of known HIV infection was associated with higher IL-6 levels. Frailty was independently associated with higher CRP levels, and risk of malnutrition and COPD with higher sCD14 levels. VACS mortality risk remained independently associated with IL-6, VCAM-1, sCD163 and I-FABP. Global DNA methylation showed more limited associations, with serum albumin remaining independently associated in multivariable analysis.