Study of viral and immunological features of HIV-related leukoencephalopathies in HAART-treated patients

INTRODUCTION: To investigate clinical, virological and immunological parameters and better understand the etiopathogenesis of AIDS-related leukoencephalopathies, a longitudinal survey was performed. RESULTS: Clinical observations and MRI examinations were performed on 160 eligible HIV+ HAART treated patients: 33 MRI+ and 45 MRI-patients were enrolled in the study, together with 27 healthy subjects (HC), as control. In addition a group of control constituted of 20 Relapsing-remitting (RR) Multiple Sclerosis (MS) patients has been enrolled. No virus was found in CSF of 12 patients, classified as possible Not Determined Leukoencephalopathy (NDLE) subjects and JCV DNA was found in CSF of 11 Progressive Multifocal Leukoencephalopathy (PML) patients. Stereotactic brain biopsies collected from two NDLE patients revealed the presence of JCV DNA; after several months, JCV DNA was also found in the CSF of both patients. The immunological evaluations revealed that IFNg producing CD4+ percentage, after VP1 peptides stimulation, was significantly higher (p<0.05) in PML , than in HC; IL2 producing CD4+ was significantly higher (p<0.05) in NDLE and PML than in HC; likewise, the IFNg producing CD8+ cells was higher (p<0.05) in NDLE than in HC. Moreover, we observed a significant increase of CD8+ apoptotic cell after MBP stimulation in HC in comparison to MS, NDLE and PML patients (p<0.05). CONCLUSIONS: Our findings suggest the brain as possible site of latency for JCV and that the onset of the PML pathogenesis could occur earlier than thought. Finally, JCV-specific immune response observed in PML and in NDLE indicates these immunological tests as possible surrogate markers for disease evolution.