title: Adjunctive and long-acting nanoformulated antiretroviral therapies for HIV-associated neurocognitive disorders.
abstract: OBJECTIVE
  We are pleased to review current and future strategies being developed to modulate neuroinflammation while reducing residual viral burden in the central nervous system. This has been realized by targeted long-acting antiretroviral nano and adjunctive therapies being developed for HIV-infected people. Our ultimate goal is to eliminate virus from its central nervous system reservoirs and, in so doing, reverse the cognitive and motor dysfunctions.
  
  
  RESULTS
  Herein, we highlight our laboratories' development of adjunctive and nanomedicine therapies for HIV-associated neurocognitive disorders. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory proinflammatory neurotoxic factors and signaling pathways.
  
  
  CONCLUSIONS
  Antiretroviral therapy has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HIV-associated neurocognitive disorders. Symptoms, although reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication, inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir-targeted nanoformulated antiretroviral therapy. The translation of these inventions from animals to humans is the focus of this review.
authors.affiliation: aDepartment of Pharmacology and Experimental Neuroscience, Nebraska Medical Center, Omaha, Nebraska bDepartment of Neurology, Center for Neural Development and Disease, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Harris A
authors.initials: HA
authors.lastname: Gelbard
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000821:virology; D044966:Anti-Retroviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000821:virology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000821:virology; D015658:HIV Infections / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D050997:Nanomedicine / Q000379:methods
chemical_list: D044966:Anti-Retroviral Agents