NF-κB p65 as a predictive biomarker of low-grade inflammation in ART-treated HIV-1 infection: comparison with HS-CRP

Low-grade inflammation remains a clinical concern in virally suppressed people living with HIV-1 (PWH). Identifying reliable biomarkers is essential for monitoring inflammation-related risk.

This exploratory cross-sectional study evaluated NF-κB p65 as a biomarker in 60 virally suppressed HIV-1 infected individuals and 60 controls. NF-κB p65 and high-sensitive C-reactive protein (HS-CRP) levels were quantified. Statistical analyses were performed in R (v4.3.2) using multivariable logistic regression model, adjusting for age, gender, HS-CRP, and socio-economic status. Predictive performance was assessed using AUC, calibration, and decision curve analysis. Additional analysis includes principal component analysis (PCA), k-means clustering, and linear regression was performed.

NF-κB p65 levels were significantly elevated in PWH than controls (p < 0.001), while HS-CRP was not independently associated. NF-κB p65 remained the strongest predictor of low-grade inflammation (OR = 2.3, AUC = 0.816) than HS-CRP. The model demonstrated good calibration and clinical utility. PCA and k-means clustering revealed heterogenous inflammatory profiles, and NF-κB p65 showed a borderline inverse association with CD4+ T cell counts. Low SES was also linked to increased inflammation (p < 0.001).

NF-κB p65 is a promising biomarker for monitoring subclinical inflammation in virally suppressed HIV-1 infection.