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

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