title: Antiretroviral therapy reduces neurodegeneration in HIV infection.
abstract: OBJECTIVE
  To determine the effect of virally suppressive antiretroviral therapy (ART) on cortical neurodegeneration and associated neurocognitive impairment.
  
  
  METHODS
  Retrospective, postmortem observational study.
  
  
  METHODS
  Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 HIV-infected volunteers from the general community who had never undergone ART (n = 7, 'naive') or who had undergone ART and whose plasma viral load was detectable (n = 64 'unsuppressed') or undetectable (n = 19, 'suppressed') at the last clinical visit before death. Individuals were predominately men (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections.
  
  
  RESULTS
  The suppressed group had higher SYP density than the naive group (P = 0.007) and higher MAP2 density than the unsuppressed group (P = 0.04). The suppressed group had lower odds of HIV-associated neurocognitive disorders than naive [odds ratio (OR) 0.07, P = 0.03]. Higher SYP was associated with lower likelihood of HIV-associated neurocognitive disorders in univariable (OR 0.8, P = 0.03) and multivariable models after controlling for ART and brain HIV p24 protein levels (OR 0.72, P = 0.01).
  
  
  CONCLUSIONS
  We conclude that virally suppressive ART protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes.
authors: aHIV Neurobehavioral Research Center, University of California San Diego bDepartment of Psychiatry cDepartment of Neurosciences dDepartment of Pathology, University of California San Diego, La Jolla, San Diego, California, USA.
authors: Alex K
authors: AK
authors: Bryant
authors: Ronald J
authors: RJ
authors: Ellis
authors: Anya
authors: A
authors: Umlauf
authors: Ben
authors: B
authors: Gouaux
authors: Virawudh
authors: V
authors: Soontornniyomkij
authors: Scott L
authors: SL
authors: Letendre
authors: Cristian L
authors: CL
authors: Achim
authors: Eliezer
authors: E
authors: Masliah
authors: Igor
authors: I
authors: Grant
authors: David J
authors: DJ
authors: Moore
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001344:Autopsy; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012189:Retrospective Studies; D016708:Synaptophysin / Q000032:analysis; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C569014:SYP protein, human; D016708:Synaptophysin