Patient-Level Discordance Between SCORE2 Cardiovascular Risk and PD-1/PD-L1 Checkpoint-Expression Profiles in People Living with HIV: A Secondary Cohort Analysis

Background: Conventional cardiovascular risk scores do not directly characterize immune checkpoint-expression phenotypes in people with HIV. We examined patient-level alignment between SCORE2 and PD-1/PD-L1 checkpoint expression in a secondary analysis of a previously characterized parent cohort. Methods: Data from 100 PWH followed at a single HIV center were analyzed. SCORE2, lipid parameters, systolic blood pressure, CD4+/CD8+ ratio, and flow-cytometric PD-1/PD-L1 expression on T-cell, B-cell, and NK-cell subsets were assessed at baseline and after 12 months. Composite immune-exhaustion indices were derived from standardized checkpoint-marker values. Discordance profiles were defined using quartile thresholds for endpoint SCORE2 and immune exhaustion. Results: Smokers had higher endpoint SCORE2 than nonsmokers (median 3.5% vs. 1.0%; p = 0.001), but smoking was not associated with higher composite or individual checkpoint-defined exhaustion. Endpoint SCORE2 correlated with classical cardiovascular variables but not with the composite exhaustion index (ρ = 0.075; p = 0.468) or individual PD-1/PD-L1 markers. Discordant cardiovascular–immune profiles were observed in 10 of 96 evaluable participants (10.4%). Conclusions: SCORE2 and PD-1/PD-L1 checkpoint-expression profiles showed limited contemporaneous alignment in this cohort. The identified discordant profiles are exploratory and require external validation.