JC virus DNA in cerebrospinal fluid of human immunodeficiency virus—infected patients: Predictive value for progressive multifocal leukoencephalopathy

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Abstract
Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell‐mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV ‐ 1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV‐1‐positive patients with PML, 114 HIV‐1‐positive control subjects, and 16 control subjects who were HIVv1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 μl of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML: 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV‐infected patients and one from an HIVvnegative patient with risk factors for PML and an unexplained hemiparesis. Overall senstivity was 92% (24/26); specificity was, at minimum, 92% (119/130). Treatments for PML are now in clinical trials. This assay provides a safe, inexpensive means of establishing the diagnosis of a potentially treatable condition. Furthermore, our data suggest that a subgroup of presymptomatic patients who may be at high risk for PML can be identified. Such patients may be particularly suitable for prophylactic interventions.