title: Peripheral blood mononuclear cells HIV DNA levels impact intermittently on neurocognition.
abstract: OBJECTIVE
  To determine the contribution of peripheral blood mononuclear cells' (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV-associated neurocognitive disorders (HAND) in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART).
  
  
  METHODS
  Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.
  
  
  RESULTS
  At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05). Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 106 PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04), and higher in those with no ART treatment during HIV infection 1st year (p = .03). Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor-coordination (p = .02-.12) to a lesser extent.
  
  
  CONCLUSIONS
  PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.
authors: Neuroscience Research Australia, Sydney, Australia; Peter Duncan Neurosciences Unit, St. Vincent's Centre for Applied Medical Research, Sydney, Australia; The University of New South Wales (UNSW), Sydney, Australia.
authors: Lucette A
authors: LA
authors: Cysique
authors: The Kirby Institute, UNSW Medicine, UNSW Australia, Sydney, Australia; The University of New South Wales (UNSW), Sydney, Australia.
authors: William J
authors: WJ
authors: Hey-Cunningham
authors: Neuroscience Research Australia, Sydney, Australia; Macquarie University, Sydney, Australia.
authors: Nadene
authors: N
authors: Dermody
authors: Departments of Neurology and HIV, St. Vincent's Hospital, Darlinghurst, Sydney, Australia; Queen Elizabeth Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors: Phillip
authors: P
authors: Chan
authors: Peter Duncan Neurosciences Unit, St. Vincent's Centre for Applied Medical Research, Sydney, Australia; Departments of Neurology and HIV, St. Vincent's Hospital, Darlinghurst, Sydney, Australia; The University of New South Wales (UNSW), Sydney, Australia.
authors: Bruce J
authors: BJ
authors: Brew
authors: The Kirby Institute, UNSW Medicine, UNSW Australia, Sydney, Australia; Departments of Neurology and HIV, St. Vincent's Hospital, Darlinghurst, Sydney, Australia; The University of New South Wales (UNSW), Sydney, Australia.
authors: Kersten K
authors: KK
authors: Koelsch
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D004279:DNA, Viral / Q000097:blood*; D003704:Dementia / Q000097:blood / Q000503:physiopathology / Q000821:virology; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral