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.
Bossolasco
Simona
S
Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Calori
Giliola
G
Moretti
Francesca
F
Boschini
Antonio
A
Bertelli
Davide
D
Mena
Maurizio
M
Gerevini
Simonetta
S
Bestetti
Arabella
A
Pedale
Rosa
R
Sala
Serena
S
Sala
Stefania
S
Lazzarin
Adriano
A
Cinque
Paola
P
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000134:cerebrospinal fluid*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology / Q000821:virology*; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral