Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy: effects on cerebrospinal fluid markers of JC virus replication and immune response.

Abstract

Cerebrospinal fluid (CSF) samples were examined from 7 patients infected with human immunodeficiency virus type 1 (HIV-1) who had progressive multifocal leukoencephalopathy (PML). Samples were obtained both before and after 35-365 days of highly active antiretroviral therapy (HAART). By polymerase chain reaction, JC virus (JCV) DNA was found in 6 of 7 patients at baseline but in only 1 patient after HAART. In contrast, in 25 historical control patients from whom sequential CSF specimens were obtained, no reversion from detectable to undetectable JCV DNA was observed. By use of enzyme-linked immunosorbent assay, intrathecal production of antibody to JCV-VP1 was shown in only 1 of 4 HAART recipients at baseline but in 5 of 5 patients after treatment. The neuroradiological picture improved or had stabilized in all patients after 12 months of HAART, and all were alive after a median of 646 days (range, 505-775 days). Prolonged survival after HAART for PML is associated with JCV clearance from CSF. JCV-specific humoral intrathecal immunity may play a role in this response.