PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY AFTER INITIATION OF HIGLY ACTIVE ANTIRETROVIRAL THERAPY AND BENIGN EVOLUTION IN TWO HIV-1 POSITIVE PATIENTS

INTRODUCTION: Since the onset of demyelination is unpredictable, description of new cases of HIV-associated leukoencephalopathy is needed to draw a profile of their pathogenesis. METHODS: From September 2003 to April 2005 two HIV-1 infected patients were evaluated and followed-up (FU). Peripheral blood, CSF and a stereotactic cerebral biopsy of both patients were collected at different times. MRI was also performed at baseline and at least every three months. PCR analysis of specimens were performed for detecting Polyomavirus and Human Herpesviruses DNA. PBMC proliferation assay and cytokines (TNF-, IFN- and IL-2) production by PBMC were evaluated by flow cytometry, before and after VP1 JCV HLA-restricted peptides stimulation. RESULTS: Benign evolution of the PML was observed in both patients. JCV DNA was detected in stereotactic biopsies some months before than in CSF. The increase of specific IFN- producing cytotoxic CD8+ T cells at base line was shown in the stimulated PBMC sample of the patients. CD4+ cell functionality was confirmed by specific producing IFN- CD4+ T cells, highly increased during FU. DISCUSSION: Our findings suggest that the onset of PML could occur earlier than thought, and the brain could be possible site of latency of Polyomavirus. Immunological data demonstrated that specific tests might be surrogate to understand the evolution of the disease since we observed an immunological response to JCV before verifying its replication in CSF, indicating that T cell-memory response could be a marker of brain viral activity. Prolonged survival time could be associated with restoration of JCV antigen-specific T cells function.