Expression of human immunodeficiency virus in cerebrospinal fluid of children with progressive encephalopathy

Abstract

The retrovirus that causes acquired immune deficiency syndrome (AIDS) is now designated the human immunodeficiency virus (HIV). The cerebrospinal fluid (CSF) of 27 children with HIV infection was assayed for intra-blood-brain barrier (IBBB) synthesis of HIV-specific antibodies and for the presence of HIV antigen. In this cohort, 11 children had a progressive encephalopathy (PE), 9 had a static encephalopathy (SE), and 7 had normal neurological findings (N). IBBB synthesis of HIV-specific antibodies was identified (using matched serum and CSF specimens) in 7 of 11 children with PE, 4 of 9 children with SE, and 2 of 7 children with N. HIV antigen was found (using a highly sensitive solid-phase enzyme immunoassay) in the CSF of 8 of 11 children with PE, none of the children with SE, and none of the 7 children with N. On the basis of these data, we conclude that: IBBB synthesis of HIV antibodies indicates invasion of the central nervous system but may reflect prior or current infection; and HIV antigen in CSF indicates viral expression and correlates with the occurrence of PE. These findings strongly implicate HIV as the causative agent of PE in these children. The assay for HIV antigen in the CSF may be of value in determining the prognosis of children with HIV infection and for evaluating the efficacy of therapeutic agents against this retrovirus.

Intra-blood-brain barrier synthesis of human immunodeficiency virus antigen and antibody in humans and chimpanzees.

“…In cerebrospinal fluid (CSF), lIIV-Ag appears to be associated with progressive encephalopathy in children (12). In the present study, we report the correlation between HIV-Ag expression in CSF of humans and experimentally infected chimpanzees, intra-blood-brain barrier production of HIVAb, and clinical disease.…”

Human immunodeficiency virus type 1 infection of the brain

“…Although some studies have indicated that the presence of CSF HIV-1 p24 antigen is associated with a progressive encephalopathy in children (101,143) and in some adults (142), subsequent studies have failed to confirm that the detection of CSF HIV-1 antigen predicts subsequent neurological deterioration (38,296). Similarly, the isolation of HIV-1 from CSF is not a useful marker for HIV-1 encephalopathy (38).…”

Neurologic Manifestations of Pediatric Acquired Immunodeficiency Syndrome: Clinical Features and Therapeutic Approaches

“…12 These abnormalities as well as the production within the blood-brain barrier of antibodies recognizing HIV-1 have been identified in both symptomatic and asymptomatic HIV-1 infected children. 16 Children with progressive encephalopathy will, in addition, show the presence of HIV-1 p24 antigen in the CSF.I6 This, unfortunately, occurs too late in the course of disease to be of value progno~tically.~~'~…”