title: HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment.
abstract: In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Saylor
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Dickens
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Haughey
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Slusher
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Pletnikov
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Brown
authors.affiliation: The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, New York 10029, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Volsky
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6113, 600 N Wolfe St, Baltimore, Maryland 21287, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D006801:Humans; D009422:Nervous System Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents