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

Cerebrospinal fluid (CSF) samples were examined from 7 patients infected wi th human immunodeficiency virus type 1 (HIV-1) who had progressive multifoc al leukoencephalopathy (PML), Samples were obtained both before and after 3 5-365 days of highly active antiretroviral therapy (HAART), By polymerase c hain 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 pa tients from whom sequential CSF specimens were obtained, no reversion from detectable to undetectable JCV DNA was observed. By use of enzyme-linked im munosorbent 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 tr eatment. The neuroradiological picture improved or had stabilized in all pa tients after 12 months of HAART, and all were alive after a median of 646 d ays (range, 505-775 days). Prolonged survival after HAART for PML is associ ated with JCV clearance from CSF. JCV-specific humoral intrathecal immunity may play a role in this response.