In the highly active antiretroviral therapy (HAART) era, the role of the inflammatory response in acquired immunodeficiency syndrome (AIDS)-related progressive multifocal leukoencephalopathy (PML) remains controversial. In this study, JC virus DNA load and levels of cytokines were determined in cerebrospinal fluid (CSF) from 32 human immunodeficiency virus (HIV)-1-infected patients with confirmed PML who underwent HAART; cytokines were also measured in 12 HIV-positive controls. Predictors of survival were analyzed by Cox's models. Macrophage chemoattractant protein (MCP)-1 levels were significantly higher in PML patients than in controls (mean +/- SD, 2.45 +/- 0.64 versus 1.32 +/- 0.64 log(10) pg/ml, P<.0001). In PML patients, the higher concentration of MCP-1 correlated with lower JC viral load (r=-.405, P=.036). Higher concentrations of MCP-1 in CSF were associated with longer survival on HAART after adjusting for CD4 counts (for each log(10) pg/ml higher, hazard ratio for death 0.28, 95% confidence interval 0.08--1.00). Predictors of shorter survival were lower baseline CD4 counts, higher JCV DNA concentrations, lower Karnofsky, and no prior HAART exposure. These results showed that higher CSF levels of MCP-1, an inflammatory cytokine, were correlated with better prognosis in HAART-treated patients with PML.