Pathogenesis of Leukoencephalopaties in HIV positive patients treated with Highly Active Antiretroviral Therapy

INTRODUCTION: The use of HAART in the treatment of HIV infection has led to a marked reduction in AIDS-associated morbidity and mortality, but PML is still observed with a relevant prevalence in AIDS patients. Interestingly, several PML cases show a prolonged survival, moreover, a new PML-like leukoencephalopathy, called non- determined leukoencephalopathy (NDLE), without evidence of JCV active infection, has been reported. METHODS: To study the pathogenesis of these HIV-associated leukoencephalopathies, we are performing 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 16 patients with suspected NDLE, and, as controls, 29 HIV+ patients without any neurological disorders and 4 healthy subjects. RESULTS: 4 out of 16 patients were defined as PML since we found, in CSF, JCV DNA, whose VP1 and TCR region were sequenced; for 5 patients, other neurological disorders were diagnosed, on the basis of MRI results. In addition, VZV DNA was found in CSF from a patient with subacute encephalitis. All the other 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. On the basis of the immunological results we hypothesize that an imbalance of the immune system plays a significant role in NDLE pathogenesis.