Quinolinic acid in the cerebrospinal fluid of children with symptomatic human immunodeficiency virus type 1 disease: relationships to clinical status and therapeutic response.

Abstract

Quinolinic acid (QUIN) is a neurotoxin implicated in the neurologic deficits associated with human immunodeficiency virus type 1 (HIV-1) infection. Forty children with symptomatic HIV-1 disease had elevated (P < .001) cerebrospinal fluid (CSF) QUIN levels (55.8 +/- 8.9 nM) compared with controls (14.9 +/- 3.0 nM). Age-adjusted CSF QUIN concentrations in HIV-1-infected children were predicted by the general index of mental abilities (GIMA, from an age-appropriate intelligence test; r = -0.45, P < .01). Zidovudine therapy reduced CSF QUIN from 64.1 +/- 16.3 to 19.7 +/- 5.2 nM (P < .01; N = 16) and increased GIMA from 76.8 +/- 5.2 to 87.2 +/- 6.3 (P < .001). Encephalopathic HIV-1-infected patients had higher CSF QUIN levels than patients without encephalopathy (79.6 +/- 16.1 vs. 32.7 +/- 6.7 nM, P < .01). CSF QUIN concentrations were also higher (P < .001) in patients who died < or = 3 years after their baseline assessment, compared with those who were still alive. These results warrant further investigation of CSF QUIN in HIV-infected children as a mediator of neurologic dysfunction and a supplemental marker of neurologic disease, particularly when combined with measures of neurocognitive functioning.