Influence of PD-1 and PD-1L Immune Exhaustion Receptors on Immune Reconstruction in People Living With HIV.

Abstract

Introduction: The progressive immunological impairment associated with human immunodeficiency virus (HIV) infection is partially mediated by the programmed cell death protein-1 (PD-1)/programed death-ligand 1(PD-L1) inhibitory pathway. This investigation aims to evaluate the influence of PD-1 on immune reconstitution in patients undergoing antiretroviral therapy (ART), with data visualized through principal component analysis (PCA).

Materials and methods: Data from 52 ART-treated individuals achieving viral suppression were analyzed over 12 months. CD4+, CD8+, CD19+, and PD-1/PD-L1 expressions were quantified via flow cytometry at baseline and after 12 months, and immune recovery was assessed at CD4+ thresholds of 500 and 800/μL and CD4+/CD8+ ratios of >0.8 and >1.0 using linear and logistic regression. PCA was applied to visualize clustering of immune recovery patterns based on PD-1/PD-L1 expression levels and immune cell counts, with statistical significance evaluated using ANOVA.

Results: The analyzed group of 52 patients was predominantly male (65.4%; n = 34). PD-1/PD-L1 expression showed modest associations with immune recovery. Higher PD-L1 expression on CD3+ T-cells at baseline was associated with a reduced likelihood of recovery to CD4+>500/μL (OR: 0.79; 95%CI: 0.62-0.99; p = 0.04). Linear regression demonstrated that increased PD-L1 on CD4+ T-cells and PD-1 on CD19+ B-cells positively correlated with higher CD4+/CD8+ ratios at follow-up (coefficient: 0.035 and 0.03, respectively; p < 0.02), while logistic regression indicated that higher PD-1 on CD3+ T-cells increased the odds of recovery to CD4+>500/μL (OR: 1.03; 95% CI: 1.0036-1.07); = 0.03). Notably, this weak signal may result from a general increase in the number of lymphocytes during therapy. PCA did not reveal significant clustering of immune recovery patterns.

Conclusion: PD-1 and PD-L1 expressions on immune cells are weakly associated with immune recovery metrics in individuals undergoing ART. Further research is needed to explore their role in immune reconstitution and potential clinical applications.