This project addresses two overarching priorities on neurobehavioral research on HIV: (1) There is a need for a time efficient, sensitive and reliable method to assess HIV-1-associated neurocognitive disorder, especially in early phases of disease when most persons are medically asymptomatic. Existing approaches involve significant tradeoffs between time taken to assess a person and likelihood of detecting impairment. The recent development of a theory-driven computerized assessment (The Cambridge Neuropsychological Test Automated Battery (CANTAB)), which has been used successfully in detecting other forms of dementia, promises to be a useful advance methodologically. (2) Until recently, progress in understanding the neuropathogenesis of HIV has been hampered by lack of an appropriate animals model. The development of a Simian immunodeficiency virus (SIV) model in which Gold and Koob are capable of performing neurobehavioral testing of animals using a modified CANTAB approach presents an unparalleled opportunity for """"""""human/infrahuman primate translation"""""""".
Aim 1 : To determine if HIV-1 infection in humans and SIV infection in monkeys produce similar neurocognitive impairments. Using human and monkey versions of CANTAB we will compare whether the qualitative features of neurobehavioral impairment are similar, and whether progression of disease is accompanied by similar generalization from a """"""""fronto-striatal"""""""" to global impairment.
Aim 2 : To determine if CANTAB is a time-efficient, reliable, informative alternative to current lengthy neuropsychological (NP) assessments to detect and monitor HIV-1 neurocognitive disorders. Method Men and women will be recruited from the HNRC (60 AIDS, 60 HIV+ non-AIDS, and 60 HIV-controls). Subjects will receive CANTAB assessment annually for 5 years. Results of CANTAB will be related to the indepth NP and neuromedical assessments performed as part of the HNRC. Pattern and time related changes in CANTAB will be compared to similar data from monkeys in the Gold/Koob project. Significance As a result of these studies, we should be able to determine whether the SIV-infected monkeys represent a suitable animal neurobehavioral model of HIV CNS disease in humans, and whether CANTAB represents a suitable substitute, or even advance over, currently available lengthier NP assessments.
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