Beyond CD4⁺/CD8⁺: NK-Cell PD-L1 Expression and Adaptive Immune Checkpoint Profiles in People with HIV

Persistent immune exhaustion despite suppressive ART is increasingly recognised in PLWH, but NK-cell involvement remains unclear. In a single-centre longitudinal cohort, 100 PLWH were evaluated at baseline and 12 months (median age 41.5 years; 56% male; 58% newly diagnosed). At the 12-month endpoint, NK-cell frequency and PD-L1 expression were analysed cross-sectionally in 89 participants in relation to CD4⁺ T- and CD19⁺ B-cell PD-1/PD-L1 expression, the CD4⁺/CD8⁺ ratio and SCORE2, using Spearman correlations with Benjamini-Hochberg correction. NK PD-L1 strongly correlated with PD-L1 on CD4⁺ (ρ=0.778, q<0.001) and CD19+ (ρ=0.684, q<0.001) cells, and moderately with B-cell PD-1 (ρ=0.365, q=0.0013). NK frequency inversely correlated with PD-L1 on CD4⁺ (ρ=-0.459, q<0.001) and CD19+ (ρ=-0.320, q=0.00545) cells and with B-cell PD-1 (ρ=-0.236, q=0.0409). No statistically significant associations with the CD4⁺/CD8⁺ ratio or SCORE2, or differences by treatment history or the INSTI-based regimens examined, were detected. These findings describe associations between NK-cell phenotype and adaptive checkpoint expression without establishing functional exhaustion.