Dynamics of virological suppression and systemic immune-inflammatory response following antiretroviral therapy in pediatric HIV infection

Abstract

Background Persistent systemic inflammation remains a hallmark of treated HIV infection and is not reliably resolved by virological suppression alone. The Systemic Immune-Inflammation Index (SII), a composite hematologic index [(neutrophil × platelet)/lymphocyte count], has emerged as a candidate inflammatory biomarker. Longitudinal SII data following antiretroviral therapy (ART) initiation in pediatric HIV are lacking. Methods This single-center retrospective paired longitudinal study included 30 pediatric patients with HIV with laboratory data at baseline and 12 months post-ART. The primary outcome was change in SII; secondary outcomes included CD4%, HIV RNA, and double-negative T-cell percentage (DNT%). Non-improvers were characterized by age, sex, ART regimen, nutritional status, and co-infection status. Paired comparisons used the Wilcoxon signed-rank test; Spearman correlation was the primary inferential method, with Pearson as a sensitivity analysis. Results Median SII declined numerically (342,637 to 250,527) but did not reach significance (p = 0.428), despite significant improvement in CD4% (p < 0.001) and HIV RNA (p < 0.001). SII failed to improve in 13/30 patients (43.3%). The baseline inverse correlation between SII and CD4% (r = −0.450, p = 0.013) was substantially attenuated at month 12 (r = −0.004, p = 0.985). A parametric correlation between ΔSII and ΔHIV RNA (r = +0.534, p = 0.002) was not confirmed on rank-based testing (ρ = +0.004), reflecting leverage from two extreme-viremia patients. The 1–2-year age group had the highest rate of SII non-improvement (75.0%); an unadjusted post-hoc comparison with the 6–11-year group yielded a nominal p value of 0.038. Female sex was more frequent among non-improvers (53.8% vs. 17.6%; p = 0.056), although the difference was not statistically significant. Genvoya® use showed a similar non-significant trend (p = 0.132). Nutritional status, herpesvirus co-infection, and virological suppression at month 12 were not significantly associated with SII trajectory. Conclusion In this pediatric HIV cohort, SII failed to improve in nearly half of patients despite successful ART, dissociating from both CD4 reconstitution and HIV RNA suppression. These findings suggest SII reflects a residual inflammatory state driven by mechanisms beyond viral replication, including ART class-specific, sex-related, and developmental factors. Routine SII monitoring may identify patients at ongoing inflammatory risk despite virological success; larger prospective studies are needed.