title: Current understanding of HIV-associated neurocognitive disorders pathogenesis.
abstract: OBJECTIVE
  The present review discusses current concepts of HIV-associated neurocognitive disorders (HAND) in the era of antiretroviral therapy (ART). As the HIV epidemic enters its fourth decade (the second decade of ART), research must address evolving factors in HAND pathogenesis. These include persistent systemic and central nervous system (CNS) inflammation, aging in the HIV-infected brain, HIV subtype (clade) distribution, concomitant use of drugs of abuse, and potential neurotoxicity of ART drugs.
  
  
  RESULTS
  Although the severest form of HAND, HIV-associated dementia (HAD), is now rare due to ART, the persistence of milder, functionally important HAND forms persist in up to half of HIV-infected individuals. HAND prevalence may be higher in areas of Africa where different HIV subtypes predominate, and ART regimens that are more effective in suppressing CNS HIV replication can improve neurological outcomes. HAND are correlated with persistent systemic and CNS inflammation, and enhanced neuronal injury due to stimulant abuse (cocaine and methamphetamine), aging, and possibly ART drugs themselves.
  
  
  CONCLUSIONS
  Prevention and treatment of HAND requires strategies aimed at suppressing CNS HIV replication and effects of systemic and CNS inflammation in aging and substance-abusing HIV populations. Use of improved CNS-penetrating ART must be accompanied by evaluation of potential ART neurotoxicity.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6146, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gannon
authors.forename: Muhammad Z
authors.initials: MZ
authors.lastname: Khan
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kolson
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D019966:Substance-Related Disorders / Q000150:complications; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents