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

Clin Infect Dis. 2005 Mar 1;40(5):738-44. doi: 10.1086/427698. Epub 2005 Feb 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • DNA, Viral / cerebrospinal fluid*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV-1
  • Humans
  • JC Virus / isolation & purification*
  • Leukoencephalopathy, Progressive Multifocal / cerebrospinal fluid
  • Leukoencephalopathy, Progressive Multifocal / diagnosis
  • Leukoencephalopathy, Progressive Multifocal / etiology
  • Leukoencephalopathy, Progressive Multifocal / virology*
  • Male
  • Prognosis
  • RNA, Viral / blood
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Viral Load


  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral