Immunovirological analysis according to outcome in AIDS-associated progressive multifocal leukoencephalopathy (PML) on combination antiretroviral therapy (CART)

Background: Despite the use of CART following PML diagnosis, the survival remains poor in about 50% of patients. Objective: To examine virological and immunological mechanisms underlying survival heterogeneity in AIDS-associated PML patients on CART. Methods: JC virus (JCV) load in CSF was determined by using quantitative PCR (37 patients). Sequencing of the region of VP1 and the transcription control region (TCR) was performed (10 patients). In parallel, proliferation of PBMC to purified JCV was examined (10 patients). Results: We found a significant negative correlation between JCV load in CSF and survival (r = -0.55, p < 10 super(-4)). All the JCV TCR sequences in CSF were rearranged. In this series of patients, no particular TCR rearrangement patterns or VP1 genotypes were found associated with poor outcome. A trend to negative correlation was found between CD4 T cell proliferation to JCV and JCV load in CSF. Conclusions: High JCV load in CSF and weak anti-JCV CD4 T cell response are associated with a poor outcome in AIDS-associated PML.