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J Infect Dis. 2013 Nov 15;208(10):1604-12. doi: 10.1093/infdis/jit388. Epub 2013 Aug 1.

Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patients with cryptococcal meningitis and cryptococcosis-associated immune reconstitution inflammatory syndrome.

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Department of Infectious Diseases, Alfred Hospital.



Human immunodeficiency virus-infected patients with treated cryptococcal meningitis who start combination antiretroviral therapy (cART) are at risk of further neurological deterioration, in part caused by paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We hypothesized that C-IRIS is associated with alterations of chemokine receptor expression on T cells and chemokine concentrations in cerebrospinal fluid (CSF) that enhance recruitment of T-helper 1 cells and/or myeloid cells to the central nervous system.


In a prospective study of 128 human immunodeficiency virus-infected patients with cryptococcal meningitis who received antifungal therapy followed by cART, we examined the proportions of CD4(+) and CD8(+) T cells expressing CCR5 and/or CXCR3, in CSF and whole blood and the concentrations of CXCL10, CCL2, and CCL3 in stored CSF and plasma.


The proportion of CD4(+) and CD8(+) T cells expressing CXCR3(+)CCR5(+) and the concentrations of CXCL10, CCL2 and CCL3 were increased in CSF compared with blood at cART initiation (P < .0001). Patients with C-IRIS (n = 26), compared with those with no neurological deterioration (n = 63), had higher CSF ratios of CCL2/CXCL10 and CCL3/CXCL10 and higher proportions of CXCR3(+)CCR5(+)CD8(+)T cells in CSF compared with blood at cART initiation (P = .03, .0053, and .02, respectively).


CD8(+) T-cell and myeloid cell trafficking to the central nervous system may predispose patients to C-IRIS.


HIV; chemokines; cryptococcus; immune restoration disease

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