title: The effects of HIV and combination antiretroviral therapy on white matter integrity.
abstract: OBJECTIVE
  HIV preferentially affects white matter in the brain. Although combination antiretroviral therapy (cART) reduces HIV viral load within the brain, continued inflammation can persist. We investigated the effect of HIV and cART on white matter integrity.
  
  
  METHODS
  We used diffusion tensor imaging (DTI) to examine the effects of HIV and cART on white matter integrity within the corpus callosum and centrum semiovale (CSO).
  
  
  METHODS
  Neuropsychological testing and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity) were obtained from 21 HIV-uninfected controls, 21 HIV-infected patients naive to cART (HIV+/cART-), and 21 HIV+ patients receiving stable cART (HIV+/cART+). A subset of the HIV+/cART- individuals (n=10) was assessed before and 6 months after receiving medications. Differences among the cross-sectional groups were assessed using an analysis of variance, whereas paired t-tests evaluated longitudinal changes.
  
  
  RESULTS
  HIV+/cART- participants had significantly lower mean diffusivity, axial diffusivity, and radial diffusivity for the corpus callosum and CSO compared to HIV- controls and HIV+/cART+ individuals. No significant difference existed between HIV- controls and HIV+/cART+ patients. cART initiation significantly improved mean diffusivity, radial diffusivity, and axial diffusivity, but not fractional anisotropy, in the corpus callosum and CSO in some HIV-infected patients.
  
  
  CONCLUSIONS
  Observed decreases in DTI parameters between HIV+/cART+ and HIV+/cART- individuals could reflect the presence of inflammatory cells or cytotoxic edema in HIV+/cART- patients. Initiating cART could lead to a reduction in neuro-inflammation and improvement in DTI measures. Future DTI studies may be useful for evaluating the efficacy higher brain penetrating cART regimens.
authors.affiliation: Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Wright
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Heaps
authors.forename: Josh S
authors.initials: JS
authors.lastname: Shimony
authors.forename: Jewell B
authors.initials: JB
authors.lastname: Thomas
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D054022:Cerebrum / Q000187:drug effects / Q000473:pathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D056784:Leukoencephalopathies / Q000150:complications / Q000473:pathology*; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D044966:Anti-Retroviral Agents