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HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY:EFFECT ON CEREBROSPINAL FLUID MARKERS OF JC VIRUS REPLICATION AND IMMUNE RESPONSE
Immune response
Antiretroviral therapy
Highly active
Drug clearance
DNA
Hiv-1
jc virus
Progressive multifocal leukoencephalopathy
Cerebrospinal fluid
Author
Affilliation
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Neurology Clinic. Marienkrankenhausen, Hamburg, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Clinic of Infectious Diseases. Spedali Civili, Brescia, Italy.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
German Primate Center. Department of Virology and Immunology. Go¨ttingen, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Neurology Clinic. Marienkrankenhausen, Hamburg, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Neurology Clinic. Marienkrankenhausen, Hamburg, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Clinic of Infectious Diseases. Spedali Civili, Brescia, Italy.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
German Primate Center. Department of Virology and Immunology. Go¨ttingen, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
Neurology Clinic. Marienkrankenhausen, Hamburg, Germany.
San Raffaele Hospital. Division of Infectious Diseases. Milan, Italy.
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.
Keywords
Polymerase chain reactionImmune response
Antiretroviral therapy
Highly active
Drug clearance
DNA
Hiv-1
jc virus
Progressive multifocal leukoencephalopathy
Cerebrospinal fluid
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