Clinical and Virological Monitoring During Treatment with Intrathecal Cytarabine in Patients with AIDS‐Associated Progressive Multifocal Leukoencephalopathy

Abstract

We describe the clinical and virological outcome of human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy (PML) treated with cytarabine. Twenty-seven patients received intrathecal cytarabine, 5 received concomitant intravenous cytarabine, and 20 received concomitant antiretroviral therapy. The median baseline CD4+ cell count was 28/mm3. After 4 weeks, 4 (19%) of 21 evaluable patients had stable disease, whereas the others progressed. The median survival from diagnosis and from onset was 66 and 128 days, respectively. Patients with Karnofsky scores of >50 and those previously taking antiretroviral medications had a higher probability of survival 3 months after diagnosis (P = .003 and P = .05, respectively). Overall, after 4 weeks, median JC virus load in CSF increased by 0.7 log10 copies/mL from baseline (P = NS). The mean JC virus load at 4 weeks was lower in patients with stable disease than in progressors (3.47 vs. 4.47 log10 copies/mL; P = .027). JC virus became undetectable in the only patient who had a long-term stable condition. The concentration of JC virus in CSF showed a correlation with clinical outcome.

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

“…In HIV-infected hosts, the clinical course of PML is almost invariably fatal and there is no proven effective therapy for this condition. Initial anecdotal reports of responses to cytarabine (cytosine arabinoside) have not been confirmed in larger or randomized trials (78). If, however, cytarabine was combined with cidofovir, a remarkable turnaround of PML was noted in a patient with advanced HIV disease (27); cidofovir may well have been the major factor contributing to the successful resolution of PML in this patient (27).…”

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

“…Detection of JCV DNA by qPCR and the copy number of viral DNA can be used for diagnosis in conjunction with clinical and radiographic findings. Patients with lower, or decreasing, levels of JCV genomes in the CSF after therapy may show better longevity (108,109), but the prognostic significance of the viral load of JCV in the CSF has not yet been fully established (51).…”

Reduced Rate of Diagnostic Positive Detection of JC Virus DNA in Cerebrospinal Fluid in Cases of Suspected Progressive Multifocal Leukoencephalopathy in the Era of Potent Antiretroviral Therapy

“…At the rim of these foci, virus accumulates to high concentrations in oligodendrocytes causing their destruction by cytolysis (6). Before the advent of highly active antiretroviral therapy (HAART), PML was characterized by an extremely poor disease prognosis (10). The definitive diagnosis of PML is based on the concomitant presence of a compatible clinical and neuroimaging picture and characteristic histopathologic features with JC virus detection in the brain tissue (11,12).…”