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Clinical and mycological predictors of cryptococcosis-associated Immune reconstitution inflammatory syndrome (C-IRIS).

Chang CC, Dorasamy AA, Gosnell BI, Elliott JH, Spelman T, Omarjee S, Naranbhai V, Coovadia Y, Ndung'u T, Moosa MY, Lewin SR, French MA
aDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia bDepartment of Infectious Diseases, King Edward VIII Hospital, University of KwaZulu Natal (UKZN), Durban, South Africa cHIV Pathogenesis Programme, Doris Duke


OBJECTIVE:: HIV-infected patients with treated cryptococcal meningitis (CM) are at risk of further neurological deterioration (ND) after commencing combination antiretroviral therapy (cART), mostly due to cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification strategies. DESIGN:: Prospective, longitudinal cohort study for 24 weeks. SETTING:: Durban, South Africa. SUBJECTS:: 130 HIV-infected patients experiencing first episode of CM. INTERVENTION:: Antifungal therapy (Amphotericin 1 mg/kg median 14 days, followed by consolidation and maintenance fluconazole) and cART (commenced median of 18 days from CM diagnosis). MAIN OUTCOME MEASURE:: Rate of C-IRIS and clinical, blood and CSF markers associated with C-IRIS before and during ART. 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%) ND-not C-IRIS and 63 (59.4%) no-ND. On multivariable analysis, lower CD4+ T-cell increases on cART (Hazard ratio HR 0.99, p = 0.026), persistent CSF cryptococcal growth (HR 0.27, p = 0.026) and lower CSF protein (HR 0.53, p = 0.059) prior to cART initiation were associated with C-IRIS. Using survival analysis, patients with a negative cryptococcal culture pre-cART commencement (n = 51; 48.1%) experienced fewer episodes of ND, C-IRIS and cryptococcal relapse/persistence than patients with a positive CSF culture (n = 55; 51.9%, HR 0.33, 0.33 and 0.12 and p = 0.0003, 0.0042 and, 0.0004, respectively). CONCLUSIONS:: 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.

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  • Journal: AIDS
  • Published: 21/03/2013
  • Volume: 27
  • Issue: 13
  • Pagination: 2089-2099