Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients with HIV-associated progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) remains a frequent and life-threatening complication of human immunodeficiency virus (HIV) infection in the era of highly active antiretroviral therapy (HAART). Although one-half of patients with this disease will survive, the outcome is unpredictable at diagnosis, and prognostic markers are needed. METHODS: JC virus (JCV) DNA levels were measured in cerebrospinal fluid (CSF) samples obtained from 61 HIV-infected patients with PML, including 38 patients who were treated with HAART and 23 patients who did not receive HAART, with use of real-time polymerase chain reaction. The diagnostic reliability of the assay was evaluated by comparing CSF findings with histopathological findings in patients with PML or other HIV-related diseases of the central nervous system. The prognostic value was assessed by comparing JCV DNA levels with survival and other patient variables. RESULTS: The assay had a diagnostic sensitivity of 76% and specificity of 100%. In the first CSF sample obtained after onset of PML symptoms, JCV DNA values ranged from undetectable to 7.71 log copies/mL (median, 3.64 log copies/mL). JCV DNA levels >3.64 log copies/mL correlated significantly with shorter survival and lower CD4+ cell counts in patients not receiving HAART. However, neither relationship was found in patients who were treated with HAART. The analysis of sequential CSF samples obtained from 24 patients demonstrated a marked decrease in JCV DNA levels over time in HAART-treated patients showing PML stabilization, but not in untreated or HAART-treated patients with progressively fatal disease. CONCLUSIONS: Measurement of JCV DNA levels in CSF samples may be a useful virological marker for management of PML in patients receiving HAART.