Beyond traditional criteria: CRP and fibrinogen as biomarkers of metabolic syndrome in ART-treated people living with HIV and their association with HIF-1α rs11549465

<jats:p> Metabolic syndrome (MS) is highly prevalent among people living with HIV (PLWH) receiving antiretroviral therapy (ART) and is driven by persistent low-grade inflammation. Hypoxia-inducible factor 1 alpha ( <jats:italic>HIF-1α</jats:italic> ) polymorphisms may influence inflammatory pathways underlying MS. This study investigated the association of the rs11549465 <jats:italic>HIF-1α</jats:italic> polymorphism with inflammatory markers and MS in PLWH receiving ART. We conducted a multicenter case-control study including 116 PLWH treated at two University Clinical Centers in Serbia. Participants were classified according to NCEP ATP III criteria. Genotyping was performed by Real-Time PCR using TaqMan assays. C-reactive protein (CRP) and fibrinogen levels were significantly higher in participants with MS (p &lt; 0.05). ROC analysis demonstrated their potential as biomarkers of MS with cut-off values of 1.85 mg/L for CRP and 2.49 g/L for fibrinogen. Age significantly correlated with CRP and Neutrophil/Lymphocyte ratio (p &lt; 0.05). Elevated CRP and fibrinogen levels were associated with hypertension, hypertriglyceridemia, and other MS-abnormalities (p &lt; 0.05). The <jats:italic>HIF-1α</jats:italic> rs11549465 CT + TT genotype was associated with higher IL-6 levels among participants with MS (p = 0.026). CRP and fibrinogen may complement existing MS criteria in identifying PLWH at increased risk of cardiovascular disease and diabetes. These findings highlight the role of chronic inflammation and genetic variability in metabolic complications of HIV. </jats:p>