Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) characterized by widespread lesions due to infection of oligodendrocytes by JC virus, which is a human polyomavirus (formerly known as papovavirus). It is a small non-enveloped double-stranded DNA virus that was identified as the etiological agent in 1967 and was named JC virus in 1971 after John Cunningham, from whom it was first isolated. It occurs almost exclusively in immunosuppressed individuals, e.g., patients with AIDS, hematological and lymphoreticular malignancies, autoimmune rheumatological diseases, or those having undergone organ transplantation. PML has also been reported in patients receiving immune therapy with monoclonal antibodies (eg, natalizumab, rituximab) and various other immunosuppressants, including prednisone, cyclophosphamide, methotrexate, and cyclosporine.
PML is associated with both HIV-1 and HIV-2.
HIV infection accounts for almost 85% of the total cases, and its prevalence in this population is around 4-5%.
It is currently one of the AIDS-defining illnesses in HIV-infected patients.
HIV-associated PML also occurs during immune recovery following the initiation of highly active antiretroviral therapy (HAART).
Such cases are associated with an inflammatory reaction in brain lesions and contrast enhancement on neuroimaging studies. The outcome of inflammatory PML is more variable than that of PML in end-stage AIDS.
Most patients with HIV infection develop PML in the setting of a poor immunological status expressed by a low CD4 cell count (< 200/µL). Very few reports have described of PML in HIV-infected patients in the setting of better immunological function (ie, CD4 counts >500/µL).
Recurrence of PML despite many years of immune recovery in HIV has been reported.