Abstract
OBJECTIVE: The systemic immune-inflammation index (SII) represents a promising yet underexplored biomarker in HIV-associated cryptococcal meningitis (HCM). The study aimed to assess the association between SII levels before and during treatment, and 24-week outcomes in HCM patients, as well as its potential for predicting mortality. METHODS: This was a secondary analysis of a prospective multicenter study involving HIV patients with newly diagnosed cryptococcal meningitis (CM). SII was measured at baseline, and at weeks 2 and 4 following initiation of induction antifungal therapy. Correlations between baseline SII levels and clinicopathological factors were analyzed. We also investigated the relationship that baseline and on-treatment SII levels may have on patient cumulative mortality. RESULTS: In total, 21.8% (54/248) of HCM patients succumbed within the 24-week follow-up period. Baseline SII levels were significantly higher in HCM patients compared to those with HIV without CM (p<0.0001). In patients with HCM, SII levels during treatment were significantly higher in non-survivors than in survivors. Furthermore, a negative correlation was observed between SII levels and CD4+ T-cell counts in HCM patients (r=-0.245, p<0.001). After adjusting for potential confounders, elevated SII levels at weeks 2 and 4 remained independently associated with a 2.5-fold and 5.5-fold increased risk of mortality, respectively [adjusted hazard ratio (95% CI): 2.51 (1.09-5.76), p=0.03; 5.47 (2.38-12.6), p<0.001, respectively]. Moreover, the combination of SII levels at weeks 2 and 4, as well as their integration with impaired consciousness (IC) status, effectively predicted poor outcomes within 24 weeks. CONCLUSION: Elevated SII levels during treatment are independently associated with increased 24-week mortality in HCM patients, suggesting the potential of SII as an effective prognostic biomarker. The integration of the SII into IC indicators for risk stratification further improves prognostic accuracy.