Abstract

Background. HIV-infected patients with treated cryptococcal meningitis (CM) who initiate combination antiretroviral therapy (cART) are at risk of further neurological deterioration (ND), 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 Th1 T-cells and/or myeloid cells to the central nervous system (CNS).Methods. In a prospective study of 128 HIV-infected patients with CM 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 concentrations of CXCL10, CCL2 and CCL3 in stored CSF and plasma.Results. The proportion of CD4+ and CD8+ T-cells expressing CXCR3+CCR5+ and the concentration of CXCL10, CCL2 and CCL3 were increased in CSF compared to blood at cART initiation (p<0.0001). C-IRIS patients (n=26), compared to patients with no-ND (n=63), had higher CSF ratios of CCL2/CXCL10 and CCL3/CXCL10; and higher proportions of CXCR3+CCR5+CD8+T-cells in CSF compared to blood at cART initiation (p=0.0250, 0.053, 0.0177 respectively).Conclusion. CD8+ T-cell and myeloid cell trafficking to the CNS may predispose to C-IRIS.