PATHOGENESIS OF NEW FORM OF LEUKOENCEPHALOPATHIES IN HAART TREATED HIV POSITIVE SUBJECTS

INTRODUCTION: After the introduction of HAART, the reduction of HIV related CNS disorders has been less impressive than that of other HIV-associated opportunistic infections, and the incidence of PML seems to be relatively stable. In addition, several cases of JCV negative individuals suffering from a PML-like leukoencephalopathy called non-determined leukoencephalopathy (NDLE) have been reported. METHODS: To characterize the clinical, neuroradiological and laboratory aspects of this new neurological disorder. we settled an extensive evaluation of the immune system function, of the genetic background, and virus search (JCV, HSV1/2, VZV, HCMV, EBV, HHV-6) on biological samples collected at different times of the diseases in a group of 19 patients with suspected NDLE, and, as controls, 30 HIV+ patients without any neurological disorders, and 7 healthy subjects. Moreover we found 9 HIV+ patients with other neurological diseases (OND). RESULTS: 7 out of 19 patients were defined as PML since we found, in CSF, JCV DNA, whose VP1 and TCR region were sequenced; one patient was suffering of VZV subacute encephalitis and the other 11 patients display neurological symptoms compatible with NDLE and results from PCR of the CSF did not reveal the presence of any tested neurotropic viruses, such as the controls. DISCUSSION: The data obtained on the patients so far enrolled suggest that no viruses seem to be involved in NDLE. Our finding are consistent with the hypothesis that brain damage is related to the action of immune competent cells, as consequence of HAART associated immune restoration, leading to demyelination.