Independent effects of HIV, aging, and HAART on brain volumetric measures

J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):469-77. doi: 10.1097/QAI.0b013e318249db17.


Background: Neurocognitive impairment remains prevalent in HIV-infected (HIV+) individuals despite highly active antiretroviral therapy (HAART). We assessed the impact of HIV, HAART, and aging using structural neuroimaging.

Methods: Seventy-eight participants [HIV- (n = 26), HIV+ on stable HAART (HIV+/HAART+; n = 26), HIV+ naive to HAART (HIV+/HAART-; n = 26)] completed neuroimaging and neuropsychological testing. A subset of HIV+ subjects (n = 12) performed longitudinal assessments before and after initiating HAART. Neuropsychological tests evaluated memory, psychomotor speed, and executive function, and a composite neuropsychological score was calculated based on normalized performances (neuropsychological summary Z score, NPZ-4). Volumetrics were evaluated for the amygdala, caudate, thalamus, hippocampus, putamen, corpus callosum, and cerebral gray and white matter. A 3-group 1-way analysis of variance assessed differences in neuroimaging and neuropsychological indices. Correlations were examined between NPZ-4 and volumetrics. Exploratory testing using a broken-stick regression model evaluated self-reported duration of HIV infection on brain structure.

Results: HIV+ individuals had significant reductions in brain volumetrics within select subcortical regions (amygdala, caudate, and corpus callosum) compared with HIV- participants. However, HAART did not affect brain structure as regional volumes were similar for HIV+/HAART- and HIV+/HAART+. No association existed between NPZ-4 and volumetrics. HIV and aging were independently associated with volumetric reductions. Exploratory analyses suggest caudate atrophy due to HIV slowly occurs after self-reported seroconversion.

Conclusions: HIV associated volumetric reductions within the amygdala, caudate, and corpus callosum occurs despite HAART. A gradual decline in caudate volume occurs after self-reported seroconversion. HIV and aging independently increase brain vulnerability. Additional longitudinal structural magnetic resonance imaging studies, especially within older HIV+ participants, are required.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / physiology*
  • Analysis of Variance
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Atrophy / pathology
  • Brain / drug effects
  • Brain / pathology*
  • Brain / physiology
  • Executive Function / drug effects
  • Executive Function / physiology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / physiopathology
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology