Abstract

Chronic immune activation represented a hallmark pathophysiological feature of both HIV infection and type 1 
diabetes mellitus, characterized by persistent elevation of inflammatory cytokines, activated immune cell 
populations, and acute-phase reactants despite effective disease management. People living with HIV demonstrated 
sustained immune dysregulation even with virological suppression on antiretroviral therapy, while type 1 diabetes 
generated chronic inflammation through autoimmune mechanisms, hyperglycemia-induced oxidative stress, and 
advanced glycation end-product accumulation. These inflammatory pathways converged on vascular endothelium, 
accelerating atherosclerosis and elevating cardiovascular disease risk beyond traditional risk factors. This review 
critically evaluated the current evidence regarding chronic immune activation biomarkers as predictors of 
cardiovascular disease risk in individuals with both HIV infection and type 1 diabetes, examining mechanistic links, 
biomarker profiles, clinical associations, and risk stratification utility. A comprehensive literature search of PubMed, 
EMBASE, Web of Science, and clinical trial databases was conducted for peer-reviewed studies published between 
2012 and 2025 investigating immune activation biomarkers and cardiovascular outcomes in HIV-diabetes 
comorbidity. Key biomarkers including high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor
alpha, soluble CD14, soluble CD163, D-dimer, and oxidized low-density lipoprotein demonstrate synergistic 
elevations in HIV-type 1 diabetes comorbidity, correlating with subclinical atherosclerosis, endothelial dysfunction, 
and cardiovascular events. Individuals with both conditions exhibit 3.5 to 5.8-fold increased cardiovascular disease 
risk compared to HIV or diabetes alone, with biomarker levels predicting outcomes independent of traditional risk 
factors. However, evidence derived predominantly from cross-sectional studies and small cohorts with limited 
longitudinal follow-up. Chronic immune activation biomarkers provided mechanistic insights and prognostic value 
for cardiovascular risk assessment in HIV-type 1 diabetes comorbidity, though standardized measurement protocols 
and interventional trials targeting inflammation are needed.