Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia

Howard Eliot Gendelman, Jialin C Zheng, Cynthia L. Coulter, Anuja Ghorpade, Myhanh Che, Michael Thylin, Ronald Rubocki, Yuri Persidsky, Francis Hahn, John Reinhard, Susan Swindells

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

A human immunodeficiency virus type 1 (HIV)-seropositive, antiretroviral-naive patient presented with significant cognitive dysfunction. Neuropsychologic, neuroradiologic, immunologic, and virologic studies confirmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements were demonstrated in neurologic function and were sustained for > 1 year. HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 105 to 104 copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 106 copies/mL to undetectable (< 96 copies/mL). Assays of neurotoxins (tumor necrosis factor-α, quinolinic acid, and nitric oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF demonstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversible metabolic encephalopathy fueled by viral replication. HAART used with nonsteroidal antiinflammatory agents leads to the suppression of inflammatory neurotoxins and can markedly improve neurologic function in HAD.

Original languageEnglish (US)
Pages (from-to)1000-1007
Number of pages8
JournalJournal of Infectious Diseases
Volume178
Issue number4
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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