Objective:

To investigate the relationship between mucosal and peripheral molecular signatures and clinical status, immune recovery, and ART class in virologically suppressed individuals living with HIV.

Approach:

• Study Design: Sixty-eight virologically suppressed individuals living with HIV were stratified by CDC clinical stage, ART regimen, and CD4/CD8 ratio. Targeted gene expression was assessed by RT-PCR in anorectal mucosal biopsies and peripheral blood mononuclear cells.
• Biomarker Analysis: Plasma biomarkers of epithelial injury, microbial translocation, and systemic inflammation were quantified by ELISA. Group comparisons and correlation analyses were performed using non-parametric statistics.

Key Findings:

• Distinct mucosal transcriptional patterns reflect disease stage, ART regimen, and immune recovery.
• INSTI-based therapy drives epithelial junctional remodelling toward improved barrier integrity.
• Peripheral cellular and circulating biomarkers showed limited discriminatory capacity.

Interpretation:

Mucosal analyses revealed distinct alterations associated with clinical and immunological stratifications, indicating persistent, spatially restricted epithelial–immune remodelling in treated HIV infection.

Limitations:

• The study primarily focused on individual compartments in isolation, limiting the understanding of how local epithelial perturbations translate into systemic immune activation.
• Molecular underpinnings linking epithelial gene regulation, immune signalling, and circulating biomarkers remain poorly characterized.

Conclusion:

Direct mucosal assessment is crucial to capture residual barrier and immune perturbations under suppressive ART.