Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment

Xue Hua, Christina P. Boyle, Jaroslaw Harezlak, David F. Tate, Constantin T. Yiannoutsos, Ron Cohen, Giovanni Schifitto, Assawin Gongvatana, Jianhui Zhong, Tong Zhu, Michael J. Taylor, Thomas B. Campbell, Eric S. Daar, Jeffry R. Alger, Elyse Singer, Steve Buchthal, Arthur W. Toga, Bradford Navia, Paul M. Thompson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV + patients scanned with whole-brain MRI at 1.5 T (mean age: 48.6 ± 8.4 years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4 + count, with a 1-2% white matter volume reduction for each 25-point reduction in nadir CD4 +. Even so, brain volume measured by TBM showed no detectable association with current CD4 + count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex - were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage.

Original languageEnglish
Pages (from-to)132-142
Number of pages11
JournalNeuroImage: Clinical
StatePublished - 2013
Externally publishedYes


  • Combined antiretroviral therapy
  • HIV
  • Magnetic resonance imaging
  • Nadir CD4 +
  • Proton magnetic resonance spectroscopy
  • Tensor-based morphometry


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