Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disease of the brain
caused by the JC virus (JCV). The viral genome contains a non-coding control region (NCCR) that
regulates JCV replication. In the urine of healthy people NCCR has a linear arrangement designed as
archetype (CY strain). In brain and cerebrospinal fluid (CSF) of PML patients NCCR shows deletions
and enhancements. A 51-year-old black man with HIV-1 infection was admitted to our ward because
of gait ataxia and dysarthria. Diagnosis of HIV infection was made in 2004; nadir of lymphocyte T
CD4 (CD4) count was 4 cells/μl (1%); the patient experienced multiple treatment failures; HIV
genotyping test showed a subtype B virus, with resistance mutations for PI, NRTI, NNRTI, INI and a
CXCR4 tropism. Two months before the onset of symptoms a salvage treatment with boosted
tipranavir, raltegravir, enfuvirtide, tenofovir/emtricitabine was started. At this time HIV-RNA was
2527 copies/ml and CD4 count was 9 cell/ μl (2%). After two months HIV-RNA was undetectable
and CD4 count was 23 cells/ μl (3,8%).
On admission physical examination showed a positive Romberg’s sign, gait ataxia, dysarthria and the
Kurtzke Expanded Disability Status Scale (EDSS) score was 2,5. HIV-RNA was still undetectable, CD4
count was 18 cells/ μl (4%). Brain MRI showed multiple hyperintense white matter lesions on T2-
weighted and fluid-attenuated inversion-recovery (FLAIR) imaging, in the temporal, cerebellar,
ponto-bulbar regions. Diffusion-weighted imaging (DWI) showed signal hyperintensities. No contrast
enhancement was seen. Real time polymerase chain reaction (Q-PCR) for JCV in the CSF was
positive with a viral load of 16.700 gEq/mL. HIV-RNA in CSF was undetectable. Two weeks after
admission motor function worsened and EDSS score was 6,5. A new MRI showed further extension of
the lesions previously described, with cytotoxic edema. CSF examination was repeated, with JCVDNA
viral load of 20.600 gEq/mL. An additional CSF sample was collected 4 weeks after admission,
with JCV-DNA viral load of 26.000 gEq/mL. Patient showed high level of immune activation both in
peripheral blood and CSF. Regarding the monitoring for JCV reactivation, at the time of first CSF
sampling, the patient was negative for the viral load in plasma and urine. Concerning NCCR analysis,
the viral variant archetype CY was found in CSF, in PBMCs and in the cells of the rectal swab. In the
second and third CSF samples, the JCV NCCR analysis showed the presence of a rearranged
sequence, with a duplication of the box C containing the binding site for the HIV-tat protein. In this
case we observed a rearrangement of the JCV NCCR from the first to the second CSF sample, with a
pattern suggestive for interactions between JCV and HIV-tat protein. Neurological deterioration
coincided with JCV NCCR rearrangement