SCORE2 cardiovascular risk scores and PD-1/PD-L1 checkpoint-expression profiles showed limited contemporaneous alignment in people living with HIV, with discordant cardiovascular-immune profiles observed in 10.4% of evaluable participants.
Smokers with HIV had significantly higher endpoint SCORE2 cardiovascular risk scores than nonsmokers.
Smoking status was not associated with higher composite or individual checkpoint-defined immune exhaustion.
Endpoint SCORE2 did not correlate with the composite immune exhaustion index or individual PD-1/PD-L1 markers.
Discordant cardiovascular-immune profiles were identified in approximately 10% of evaluable participants.
SCORE2 and PD-1/PD-L1 checkpoint-expression profiles showed limited contemporaneous alignment in people living with HIV.
This research examined whether a standard tool for predicting heart disease risk (called SCORE2) lines up with immune system measurements in people living with HIV. Specifically, the researchers looked at whether people with higher predicted cardiovascular risk also showed signs of immune exhaustion, measured by proteins called PD-1 and PD-L1 on immune cells. These proteins are known markers of immune cell "burnout," which is common in people with chronic HIV infection. The study followed 100 HIV-positive patients at a single clinic, measuring both cardiovascular risk factors and immune cell markers at the start of the study and again after 12 months. The main finding was that cardiovascular risk scores and immune exhaustion markers did not track together. Even though smokers had much higher cardiovascular risk scores than non-smokers (median 3.5% vs. 1.0%), smoking did not correspond to greater immune exhaustion. Overall, the statistical correlation between the cardiovascular risk score and the composite immune exhaustion measure was essentially zero (ρ = 0.075). About 10% of patients (10 out of 96) showed a notable mismatch between their cardiovascular risk profile and their immune exhaustion profile — meaning some had high cardiovascular risk but low immune exhaustion, or vice versa. This research suggests that in people with HIV, heart disease risk and immune system exhaustion are largely separate phenomena that do not reliably predict one another. This matters because clinicians managing HIV patients need to assess both cardiovascular and immune health independently, as a low cardiovascular risk score does not imply a healthy immune profile, and vice versa. The authors caution that the discordant profiles identified are preliminary and exploratory, and that larger studies at multiple sites are needed to confirm these findings.
Aksak-Wąs B, Skonieczna-Żydecka K, Cembrowska-Lech D, Parczewski M, Lewandowski F, Serwin K, et al.. (2026). Patient-Level Discordance Between SCORE2 Cardiovascular Risk and PD-1/PD-L1 Checkpoint-Expression Profiles in People Living with HIV: A Secondary Cohort Analysis.. Pathogens (Basel, Switzerland). https://doi.org/10.3390/pathogens15080871