Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Infection. 2024 Oct;52(5):1875-1887. doi: 10.1007/s15010-024-02237-6. Epub 2024 Apr 13.
The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments.
A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months.
Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78).
IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.
HIV 相关隐球菌病导致的全球死亡率显著升高,尤其是在肺部和中枢神经系统(CNS)广泛播散的重症病例中。遗憾的是,目前缺乏关于长期生存的预测分析,并且很少有研究对抗 HIV 和抗真菌治疗进行纵向随访评估。
对 83 例 HIV 相关肺和中枢神经系统播散性隐球菌病患者进行了 3 年的生存研究。对死亡和存活个体的临床和免疫参数进行了比较分析。随后,采用多变量 Cox 回归模型验证了 12、24 和 36 个月的死亡率预测。
治疗前观察到的存活组患者血浆细胞因子水平中,IL-1RA(p<0.001)和 MCP-1(p<0.05)显著降低。将 IL-1RA、IL-6 和高危 CURB-65 评分的血浆水平纳入后,预测 1 年死亡率的曲线下面积(AUC)值最高(0.96)。对于 1、2 和 3 年的预测,IL-1RA 单因素模型的表现优于所有多变量模型(AUC=0.95/0.78/0.78)。
IL-1RA 是预测 3 年生存率的生物标志物。需要进一步研究以探索 IL-1RA 在 HIV 相关播散性隐球菌病中的发病机制作用及其作为潜在治疗靶点的可能性。