Background: Although HAART has substantially improved the prognosis of progressive multi-focal leukoencephalopathy (PML), this disease is still fatal in half of the cases. Since the outcome is unpredictable at disease onset, prognostic markers are needed. Objective was to study JC virus (JCV) DNA levels in cerebrospinal fluid (CSF) of PML, HAART-treated or untreated patients (pts), and to evaluate their diagnostic and prognostic significance.

Methods: 134 CSF samples drawn from 72 HIV-infected pts with histology or laboratory-confirmed PML were retrospectively examined by a real-time polymerase chain reaction based on the TaqMan technology. HAART was started in 39, either before (n = 15) or after (n = 24) diagnosis. Magnetic resonance (MR) lesions were scored from 1 to 6 according to their number and volume.

Results: In a subgroup of 16 pts with histology-confirmed PML, JCV DNA was detected in 12, resulting in a diagnostic sensitivity of 75%. JCV DNA was found in none of 26 control pts with histologic diagnosis of other CNS diseases, giving a specificity of 100%. Overall, JCV DNA was found in 96 of 134 CSF samples, drawn from 62 of 72 PML pts (86%), ranging from < 2.00–8.82 log copies/mL (median 3.27). No correlation was found between JCV DNA levels and CD4 cells, plasma or CSF HIV-1 RNA load, either considering the patients as a whole or separated into HAART-treated or untreated, or between levels at diagnosis and MR score, ongoing HAART or survival. However, JCV DNA load inversely correlated to the distance between CSF sampling and death (p = 0.005). In HAART-treated pts there was no difference between JCV DNA levels at diagnosis and PML outcome. However, they were lower in CSF samples drawn weeks to months after PML onset and, in 14 pts with serial CSF samples, they decreased significantly in those showing disease stabilization, but not in those with progressive disease (median -2.05 vs +0.01 log copies/mL, p = 0.009).

Conclusions: Although higher CSF JCV DNA levels were found at end disease stages, levels at diagnosis did not predict PML evolution in either HAART-untreated or treated pts. In the latter, JCV DNA levels decreased with PML stabilization, suggesting a role for this marker in virological monitoring of the disease. The lack of correlation with MR lesion extension and ongoing HAART argues for the presence of complex interactions between JCV replication and the host’s immune system in the pathogenesis of PML lesions.