Skip Navigation LinksHome > August 24, 2013 - Volume 27 - Issue 13 > Clinical and mycological predictors of cryptococcosis-associ...
doi: 10.1097/QAD.0b013e3283614a8d
Clinical Science

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

Chang, Christina C.a,b,c,d; Dorasamy, Afton A.e,f; Gosnell, Bernadett I.b; Elliott, Julian H.a; Spelman, Tima,g; Omarjee, Salehac; Naranbhai, Vivekc,h; Coovadia, Yacoobe,f; Ndung’u, Thumbic; Moosa, Mohamed-Yunus S.b; Lewin, Sharon R.a,d; French, Martyn A.i,j

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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.

© 2013 Lippincott Williams & Wilkins, Inc.


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