A Cohort Study of Growth Differentiating Factor -15 (GDF-15) and Interleukin-6 (IL-6) as Biomarkers of Healthy Aging in Older Adults Living With HIV

Background: The median age of Canadians living with HIV will exceed 65 years in the next decade. Compared to HIV-negative counterparts, people living with HIV exhibit elevated serum levels of inflammatory markers. In the general population, increased levels of some markers are linked to comorbidity, frailty, cognitive decline, and mortality. To date there are no HIV-specific biomarkers to measure and monitor healthy aging or to serve as endpoints in the evaluation of relevant interventions. This study aimed to evaluate inflammatory markers as indicators of healthy aging in older people living with HIV. Methods: We analyzed data from 268 consenting participants enrolled in a sub-study of the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study. Serum samples, demographic information and healthy aging data were collected at cohort entry. Data from one participant with HIV RNA > 200/ml were excluded. Serum levels of the biomarkers CRP (C-reactive protein), D-dimer, GDF-15 (growth differentiating factor-15), and IL-6 (interleukin-6) were quantified using ELISA and compared to scores on the Rotterdam Healthy Aging Score (HAS). Statistical analyses were conducted using Spearman’s correlation. A multivariate regression model included covariates age, race, sex, years living with HIV, body mass index and CD4 count nadir. Results: Participants had a median age of 72 years (range 65-81), and were predominantly male (92%) and White (79%). They had been living with HIV for a median of 31 years and were representative of the main CHANGE HIV study cohort. The participants had a median HAS score of 12 (range 3-14). The median (IQR) for GDF-15 and IL-6 were 1810 (1310-2700) pg/ml and 3.49 (2.43-5.77) pg/ml respectively. GDF-15 and IL-6 levels were negatively associated with the HAS (R = -0.350 and –0.273), p<0.001 for both comparisons. The correlation persisted after adjustment for covariates. CRP (median 1.75, IQR 0.711, 4.29) ug/ml and D-Dimer (median 0.362, IQR 0.209-0.846) ug/ml did not show a clear association with HAS. Conclusions: Our results support the further evaluation of GDF-15 and IL-6 as potential biomarkers for healthy aging in older adults living with HIV with future studies testing the clinical utility of GDF-15 and IL-6 as outcomes in clinical care and in interventional studies. Trial Registration: Clinical trial number not applicable.