Background: Over the past three decades, the clinical presentation of HIV
infection of the Central Nervous System (CNS) has evolved. Prior to wide spread use
of effective antiretroviral therapy (ART), more than a third of infected individuals
exhibited a range of neurocognitive and motor deficits that frequently progressed to
severe dementia and paralysis. However, the use of ART has significantly decreased
the prevalence of severe forms of HIV-1 associated neurocognitive disorders
(HAND). Studies of neurocognitive dysfunction have reported variable prevalence,
ranging from 21% to 77.6%, defined primarily by mild to moderate neurocognitive
impairment. HIV-associated chronic inflammation and associated neurotoxicity of
long term ART, as well as the aging of the HIV-infected population, likely influence
the pathogenesis of HAND. Despite significant research efforts directed towards a better understanding
of the mechanisms underlying HIV neuropathogenesis, definitive causal pathophysiology of HAND and
thus effective prevention or treatment remain elusive. Furthermore, HIV therapeutic research now
includes efforts to effect a cure, by eliminating or silencing HIV within infected cells, which must
include efforts to target the latently infected cells within the CNS.
Conclusion: Prevention and treatment of the neurological complications of HIV, and eradication of
persistent virus from the CNS compartment are major priorities for the HIV-CNS research. Here we
give an overview of the progress of research on HIV-CNS disease, define new challenges and
research areas, and highlight domestic and global priorities.
Keywords: NeuroAIDS, HIV, dementia, HIV associated neurocognitive disorders, NIMH, research priorities, HAND, CNS
reservoirs, HIV cure, neuronal dysfunction, AIDS.
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