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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 10(5) to 10(4) copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 10(6) copies/mL to undetectable (< 96 copies/mL). Assays of neurotoxins (tumor necrosis factor-alpha, 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.

Five different strains of mice were investigated for their suitability to serve as models for the study of long-term effects of propoxyphene napsylate (PN) on narcotic-dependent mice. The NIH/Swiss outbred strain proved to be most suitable because of its high liability to manifest physical dependence on morphine. Following removal of subcutaneously-implanted morphine pellets from the mice, the incidence of spontaneous withdrawal jumping was used as a quantifiable criterion of physical dependence. An orally administered suspension of PN suppressed the withdrawal jumping in a dose-dependent manner. However, chronic (daily) administration of PN at doses high enough to prevent withdrawal jumping was characterized by a high degree of toxicity.