SUPPRESSION OF INFLAMMATORY NEUROTOXINS BY HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED DEMENTIA

A human immunodeficiency virus type 1 (HIV)-seropositive, antiretrovir al-naive patient presented with significant cognitive dysfunction. Neu ropsychologic, neuroradiologic, immunologic, and virologic studies con firmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements w ere demonstrated in neurologic function and were sustained for >1 year . HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 10(5) to 10(4) copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia de creased from 10(6) copies/mL to undetectable (<96 copies/mL). Assays o f neurotoxins (tumor necrosis factor-alpha, quinolinic acid, and nitri c oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF dem onstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversib le metabolic encephalopathy fueled by viral replication. HAART used wi th nonsteroidal antiinflammatory agents leads to the suppression of in flammatory neurotoxins and can markedly improve neurologic function in HAD.