PHASE III TRIAL OF 1592U89 IN HIV-1 PATIENTS WITH AIDS DEMENTIA

AIDS demetia complex (ADC), the most common manifestation of direct Human Immunodeficiency Virus (HIV) involvement in the brain is characterized by a subcortical dementia with dominant slowing of intellectual processing and poor attention. In conjunction with these complaints there are nonfocal motor abnormalities such as impaired rapid successive and alternating movements of the limbs and eyes and with progression, difficulty with balance, coordination and ambulation. To date (1996), zidovudine has been the main antiretroviral used in ADC. Though therapeutically it has been shown to enhance performance on quantitative neuropsychological testing and reduce cerebrospinal fluid (CSF) surrogate markers such as B2 microglobulin, neopoterin and quinolinic acid, the effects appear to be short lived. No other alternative treatments have been identified. The purpose of this study is to evaluate the benefit of 1592U89 succinate, a carbocylic 2,3-ene nucleoside. 90 patients will be enrolled in this multicenter phase III 12 week randomized phase followed by an optional open phase of 40 week study. The primary objectives of the study will be to evaluate the benefit on neuropsychological performance in ADC patients as well as the safety and tolerance. Secondary objectives will include examining changes in clinical dementia, neurological status, survival, AIDS defining conditions, virological and immunological markers in plasma and CSF.