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

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).

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.

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.

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.