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Although the introduction of highly active antiretroviral therapy (HAART) has prolonged and improved the lives of infected individuals, it is clear that HAART does not provide complete protection against neurological damage in HIV\/AIDS. HIV\u20101 associated dementia is a complex phenomenon, which could be the result of several mechanisms caused by those players using different intracellular signaling pathways. Understanding the causes of neurodegeneration during HIV\u20101 infection and the factors which certain individuals develop disease can provide researches on new therapeutic targets to positively affect disease outcomes. Controlling CNS viral replication with HAART is an essential primary approach, but it should be complemented with adjunctive CNS\u2010directed therapeutics. Understanding the nature of HIV\u20101 infection within the CNS as well as inflammatory responses will ultimately lead to the elimination of HIV\u2010associated neurocognitive disorders. 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