This study assessed the link between T-cell activation, differentiation and senescence phenotypes and non-AIDS-related comorbidities in HIV-suppressed patients. Patients included in the ANRS CO3 Aquitaine Cohort were consecutively enrolled in this cross-sectional study between October 2011 and May 2013 called Chronic Immune Activation and Senescence (CIADIS) study. Immune [CD4+ and CD8+ activation (DR+), differentiation (naïve and terminally differentiated memory T cells), and senescence (CD57+CD28-)] markers were summarized in a weighted immune score by principal component analysis called CIADIS. Previously described Veterans Aging Cohort Study (VACS) index and immune risk profile (IRP) scores were calculated. Adjusted logistic regression was used to assess the association between the CIADIS score and the presence of at least three non-AIDS-defining comorbidities. Only patients with plasma HIV-RNA below 40 copies/ml were analyzed. The number of comorbidities present for each patient were counted (comorbidity score) among: eGFR below 60 ml/min, diabetes, dyslipidemia, cardiovascular events, hypertension, degenerative CNS disorders, and cancer. The main outcome variable was a high comorbidity score, defined as at least 3 comorbidities.

Of 876 patients with an undetectable viral load, 73.4% were men and median age was 50.5 years [interquartile range (IQR) 44.7–56.7 years]. Median CD4 T-cell count was 579/ml (IQR 429–759 cells/ml), and median duration of HIV viral suppression was of 5.3 years (IQR 2.3–8.7). The weighted CIADIS score was associated with at least 3 comorbidities (odds ratio 1.3, 95% confidence interval 1.0, 1.6) independently of age, sex, AIDS stage, and the Veterans Aging Cohort Study score. The CIADIS and the immune risk profile scores were significantly associated with at least 3 comorbidities in adjusted models restricted to patients younger than 60 years. None of the tested scores were associated with at least three comorbidities in patients older than 60 years.

In a large assessment of cellular activation markers in patients under routine care, a significant association was found between the CIADIS score and a high comorbidity score, whereas the VACS index score as well as the IRP score were not associated with a high comorbidity score in multivariable analysis.

In conclusion, the weighted CIADIS score based on activation, senescence, and maturation markers might help physicians identifying patients at a higher risk for non-AIDS-related comorbidities.