title: Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter.
abstract: OBJECTIVE
  We evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  In this cross-sectional study, 35 HIV+ subjects aged ≥40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA <10 copies/10(6) cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV+ subjects were on combination antiretroviral therapy ≥1 year; all but 1 had plasma HIV RNA <50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV+ subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age.
  
  
  RESULTS
  Relative to the HIV+ group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (-14%, p = 0.020) and total subcortical (-10%, p = 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p < 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels.
  
  
  CONCLUSIONS
  Inability to clear peripheral blood of HIV DNA is associated with regional brain atrophy in well-controlled HIV infection, supporting the involvement of peripheral viral reservoirs in the neuropathogenesis of persistent HIV-related neurocognitive disorders.
authors.affiliation: Department of Medicine, Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA. kalpana@hawaii.edu
authors.forename: Kalpana J
authors.initials: KJ
authors.lastname: Kallianpur
authors.forename: Cecilia
authors.initials: C
authors.lastname: Shikuma
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Kirk
authors.forename: Bruce
authors.initials: B
authors.lastname: Shiramizu
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.forename: Dominic
authors.initials: D
authors.lastname: Chow
authors.forename: Scott
authors.initials: S
authors.lastname: Souza
authors.forename: Beau
authors.initials: B
authors.lastname: Nakamoto
authors.forename: Napapon
authors.initials: N
authors.lastname: Sailasuta
mesh_terms: D000328:Adult; D001284:Atrophy; D002531:Cerebellum / Q000473:pathology* / Q000821:virology; D002540:Cerebral Cortex / Q000473:pathology* / Q000821:virology; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D006679:HIV Seropositivity / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D004279:DNA, Viral