期刊
CURRENT FUNGAL INFECTION REPORTS
卷 5, 期 4, 页码 252-261出版社
SPRINGER
DOI: 10.1007/s12281-011-0064-8
关键词
HIV; AIDS; Cryptococcal meningitis; CM-IRIS; Immune reconstitution inflammatory syndrome; Pathogenesis; Review; Antiretroviral therapy; Immunology; Risk stratification; Biomarkers; Antifungal therapy; Anti-inflammatory therapy
资金
- National Institutes of Health [K23AI073192-02, U01AI089244-01]
This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th1) interferon- gamma (IFN-gamma)response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.
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