Abstract
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-γ) 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 252-261 |
| Number of pages | 10 |
| Journal | Current Fungal Infection Reports |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2011 |
Bibliographical note
Funding Information:Disclosure Conflicts of Interest: D. Wiesner: none; D. Boulware: research support from GlaxoSmithKline’s HIV Collaborative Investigator Research Award and Merck’s Investigator-Initiated Studies Program; both of these firms manufacture HIV antiretroviral medications.
Keywords
- AIDS
- Anti-inflammatory therapy
- Antifungal therapy
- Antiretroviral therapy
- Biomarkers
- CM-IRIS
- Cryptococcal meningitis
- HIV
- Immune reconstitution inflammatory syndrome
- Immunology
- Pathogenesis
- Review
- Risk stratification
