Comprehensive risk factor predictions for 3-year survival among HIV-associated and disseminated cryptococcosis involving lungs and central nervous system

• Published in: Infection Vol. 52; no. 5; pp. 1875 - 1887
• Main Authors: Wu, Luling, Fu, Xuemin, Pütz, Benno, Zhang, Renfang, Liu, Li, Song, Wei, Weng, Ling, Shao, Yueming, Zheng, Zhihang, Xun, Jingna, Han, Ximei, Wang, Ting, Shen, Yinzhong, Lu, Hongzhou, Müller-Myhsok, Bertram, Chen, Jun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2024; Springer Nature B.V
• Subjects: Adult; AIDS-Related Opportunistic Infections - microbiology; AIDS-Related Opportunistic Infections - mortality; Antifungal agents; antiretroviral agents; Biomarkers; Central nervous system; Cohort Studies; Comparative analysis; Cryptococcosis; Cryptococcosis - drug therapy; Cryptococcosis - mortality; Family Medicine; Female; Fungicides; General Practice; HIV; HIV Infections - complications; HIV Infections - mortality; Human immunodeficiency virus; Humans; Immunology; infection; Infectious Diseases; Interleukin 1 receptor antagonist; Interleukin 1 receptors; interleukin-6; Internal Medicine; Lung - microbiology; Lung - pathology; Lung diseases; Lung Diseases, Fungal - microbiology; Lung Diseases, Fungal - mortality; Lungs; Male; Medicine; Medicine & Public Health; Middle Aged; Monocyte chemoattractant protein 1; Mortality; Nervous system; Performance prediction; Plasma levels; Predictions; Regression analysis; Regression models; Risk Factors; Survival; Survival Analysis; Therapeutic targets; therapeutics; HIV/AIDS; Disseminated cryptococcosis; Three-year survival-related predictions; Antiretroviral and antifungal drug therapies
• DOI: 10.1007/s15010-024-02237-6
• ISSN: 0300-8126; 1439-0973

Background 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. Methods 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. Results 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). Conclusions 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.