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Background: About 50% of HIV⁺ patients with progressive multifocal leukoencephalopathy (PML) on HAART have poor prognosis and decease during the first months of PML. Brainstem damage may occur early in the course of PML and could be a worsening factor.

Methods: A monocenter observational study of consecutive patients with virologically or pathologically proven PML was conducted at the NeuroAIDS Rehabilitation Unit (Bicetre Hospital, France) to assess the influence on survival of brainstem lesions occurring early during the course of PML. All patients received HAART after PML diagnosis (de novo or intensification of treatment). Some of them received also cidofovir. Group A included patients with no evidence of brainstem damage. Group B included patients with evidence during the first 3 months after PML diagnosis of some of the following brainstem symptoms (oculomotor palsies, stupor and clouding of consciousness, central vestibular syndrome or dysphagia). Brainstem damage was confirmed by cerebal MRI as brainstem demyelination. JCV DNA load in CSF, a previously documented prognostic factor, was measured by quantitative PCR (detection limit = 500 copies/mL). Kaplan-Meier estimates and Cox proportional hazards model were used for survival analysis. The end-date of the study was June 30, 2003.

Results: 69 eligible patients (40 in group A and 29 in group B) were admitted between July 1996 and December 2002. Both groups were similar at baseline as regards median CD4 cell count = 76/µL (IQR 24 to 132), median plasma HIV load = 5.1 log₁₀ copies/mL (IQR 4.7 to 5.4) and median CSF JCV load = 4.3 log (IQR 3.3 to  5.0), which could be measured only in 51 patients. Median survival from diagnosis was 53.2 months in group A and 4.5 months in group B (p = 0.002). One-year cumulative probability of being alive was 77% for group A and 33.5% for group B. In the Cox multivariate analysis, the presence of brainstem damage (adjusted HR = 2.53, 1.12 to 5.72) and CSF JCV load > 4.5 log (adjusted HR = 4.07, 1.63 to 10.15) were independently associated with a shorter survival. In this model, the use of cidofovir and CD4 cell count at baseline did not influence survival.

Conclusions: Early brainstem damage and CSF JCV load are strong and independent predictors of survival in HIV⁺ patients with PML treated with HAART.

Keywords: Progressive Multifocal Leucoencephalopathy; JC virus; Survival predictor