Association between gut epithelial barrier biomarkers and LDL-cholesterol in HIV-infected individuals

Human immunodeficiency virus (HIV) infection causes gut epithelial barrier dysfunction and dyslipidemia. Intestinal fatty acid-binding protein (I-FABP) and regenerating islet-derived protein 3 alpha (REG3α) are markers of gut barrier integrity. We investigated the association between these biomarkers and LDL-cholesterol (LDL-C) in HIV-infected individuals, stratified by immune status and disease duration. This cross-sectional study included 69 HIV-infected adults on antiretroviral therapy. Plasma I-FABP, REG3α, and lipid parameters were measured. Associations were evaluated using Spearman correlation in the total cohort and stratified by cluster of differentiation 4 (CD4) count (<350, 350-500, >500 cells/μL) and disease duration (≤24, 24-48, >48 months). In the total cohort (n = 50 with lipid data), neither I-FABP (rs = -0.044, P = .762) nor REG3α (rs = 0.232, P = .105) showed a significant correlation with LDL-C. However, in patients with CD4 < 350 cells/μL (n = 12), REG3α demonstrated a strong positive correlation with LDL-C (rs = 0.643, P = .024). This association was absent in patients with higher CD4 counts (350-500: rs = 0.393, P = .383; >500: rs = 0.003, P = .985). No significant associations were observed across disease duration strata. REG3α correlates with LDL-C specifically in immunocompromised HIV patients (CD4 < 350 cells/μL), suggesting that gut barrier dysfunction may influence lipid metabolism preferentially in advanced HIV disease. This finding warrants further investigation regarding cardiovascular risk stratification in this vulnerable population.