MR PREDICTORS OF RESPONSE TO HAART IN HIV DEMENTIA

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DESCRIPTION (Applicant's abstract): Among the most common and debilitating neurological complications of HIV infection is HIV dementia (HIVD) or AIDS dementia complex (ADC). The exact pathogenesis of this disorder remains a conundrum. However, infection of mononuclear phagocytes (MP) in the CNS, and the consequent inhibition of normal synthesis of neurotrophic factors, release of neurotoxic viral proteins and release of inflammatory factors, has been strongly implicated as the precipitating event. Zidovudine monotherapy and, more recently, highly active antiretroviral therapy (HAART) have both been postulated to reduce the incidence of HIVD. Zidovudine or HAART may arrest or even reverse the dementing process, at least temporarily, in many but not all patients. The means by which HAART might slow the progression of HIVD is unclear. In this study employing patients with HIVD of varying severity, carefully studied by clinical examination, neuropsychological test battery, magnetic resonance spectroscopy (MRS) and contrast-enhanced magnetic resonance imaging (MRI), we propose to test the following hypotheses: 1) specific pathogenic pathways leading to HIVD have distinct MR signatures; 2) these different pathways have different sensitivities to HAART; 3) the MR signature will predict the effectiveness of HAART in treating HIVD. Confirmation of these hypotheses will help to validate MR as a valuable probe of different pathways of HIVD pathogenesis. It will also open novel avenues for exploring the differential sensitivities of these pathways to HAART, and suggest unique therapeutic options.