Differential systemic immune-inflammation index levels in people with and without HIV infection

Background: HIV infection is linked to persistent inflammation despite effective antiretroviral therapy (ART). The Systemic Immune-Inflammation Index (SII) is a marker of inflammation in various conditions. Methods: We compared SII values between PWH and PWoH. Clinical blood laboratory data were used to calculate the SII for each participant using the formula [(Platelet count × Neutrophil count) / Lymphocyte count]. Differences in SII values between the groups were analyzed using the Wilcoxon test, and the impact potential confounders was assessed with multivariable regression models. Results: The study included 343 PWH and 199 PWoH. Age and race did not significantly differ, but sex distribution did (83.1% male in PWH vs. 55.8% in PWoH, P < 0.0001). Among PWH, median [IQR] nadir and current CD4 counts were 199 cells/μL [50, 350] and 650 [461,858], respectively. Nearly all PWH were on ART, with 97.2% achieving viral suppression. PWH had lower SII values than PWoH (327 [224, 444] vs. 484 [335,657], P = 1.35e-14). PWH also had lower neutrophils and platelets (ps < 0.001) and higher lymphocyte counts ( P = 0.001). These differences remained significant after adjusting for age, sex, and other potential confounders. Discussion: Contrary to expectations, PWH had lower SII levels, likely due to altered hematologic parameters influenced by HIV and ART. These findings suggest that SII interpretation in PWH requires consideration of unique hematologic profiles and underscore the need for further research to understand the mechanisms and clinical implications of SII in HIV management.