Clinical and mycological predictors of cryptococcosis-associated immune reconstitution inflammatory syndrome

Christina C. Chang, Afton A. Dorasamy, Bernadett I. Gosnell, Julian H. Elliott, Tim Spelman, Saleha Omarjee, Vivek Naranbhai, Yacoob Coovadia, Thumbi Ndung'U, Mohamed Yunus S. Moosa, Sharon R. Lewin, Martyn A. French

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Objective: HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy (cART), mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification. Design: Prospective, longitudinal cohort study for 24 weeks. Setting: Durban, South Africa. Participants: One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode Intervention: Antifungal therapy (amphotericin 1 mg/kg median 14 days, followed by consolidation and maintenance fluconazole) and cART (commenced median of 18 days from cryptococcal meningitis diagnosis). Main outcome measure: Clinical, blood, and cerebrospinal fluid (CSF) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement. Results: Of 106 patients commencing cART, 27 (25.5%) developed C-IRIS, 16 (15.1%) neurological deterioration-not C-IRIS, and 63 (59.4%) no neurological deterioration. On multivariable analysis, C-IRIS was associated with persistent CSF cryptococcal growth [hazard ratio (HR) 0.27, P=0.026] and lower CSF protein (HR 0.53, P=0.059) prior to cART and lower CD4+ T-cell increases (HR 0.99, P=0.026) but not change in HIV viral load during cART. Using survival analysis, patients with a negative cryptococcal culture pre-cART commencement (n=51; 48.1%) experienced fewer episodes of neurological deterioration, C-IRIS, and cryptococcal relapse/persistence than patients with culture positivity (n=55; 51.9%, HR 0.33, 0.33, and 0.12 and P=0.0003, 0.0042, and 0.0004, respectively). Conclusion: Persistent CSF cryptococcal growth at cART initiation and poor CD4+ T-cell increases on cART are strong predictors of C-IRIS. Approaches aimed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS.

Original languageEnglish
Pages (from-to)2089-2099
Number of pages11
Issue number13
StatePublished - 24 Aug 2013
Externally publishedYes


  • Cryptococcal meningitis
  • Cryptococcosis-associated immune reconstitution inflammatory syndrome
  • Immune restoration disease


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