title: HIV-1 neuroimmunity in the era of antiretroviral therapy.
abstract: Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) can affect up to 50% of infected people during the disease course. While antiretroviral therapies have substantively increased the quality of life and reduced HIV-1-associated dementia, less severe minor cognitive and motor deficits continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral immune activation, dysregulated glial immunity, and diminished homeostatic responses are the disease-linked pathobiologic events. Monocyte-macrophage passage into the CNS remains an underlying force for disease severity. Monocyte phenotypes may change at an early stage of cell maturation and immune activation of hematopoietic stem cells. Activated monocytes are pulled into the brain in response to chemokines made as a result of glial inflammatory processes, which in turn, cause secondary functional deficits in neurons. Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Kraft-Terry
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Stothert
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009457:Neuroglia / Q000276:immunology; D015213:Neuroimmunomodulation / Q000502:physiology*
chemical_list: D044966:Anti-Retroviral Agents; D018925:Chemokines