Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection

Neurology. 2014 Oct 28;83(18):1592-600. doi: 10.1212/WNL.0000000000000932. Epub 2014 Sep 26.


Objective: We examined the longitudinal effects of primary HIV infection (PHI) and responses to early antiretroviral therapy (ART) on the brain using high-field magnetic resonance spectroscopy (MRS).

Methods: Cerebral metabolites were measured longitudinally with 4T proton MRS and assessed for ART effects in participants with PHI. Levels of glutamate (Glu), N-acetylaspartate (NAA), myo-inositol (MI), and choline-containing metabolites (Cho) were measured relative to creatine + phosphocreatine (Cr) in anterior cingulate, basal ganglia, frontal white matter, and parietal gray matter.

Results: Fifty-three participants recruited at median 3.7 months post HIV transmission were followed a median 6.0 months. A total of 23 participants initiated ART during follow-up. Prior to ART, increases per month were observed in Cho/Cr (slope = 0.0012, p = 0.005) and MI/Cr (slope = 0.0041, p = 0.005) in frontal white matter as well as increases in MI/Cr (slope = 0.0041, p < 0.001) and NAA/Cr (slope = 0.0024, p = 0.030) in parietal gray matter. After initiation of ART, prior positive slopes were no longer significantly different from zero, while Glu/Cr in basal ganglia decreased (slope = -0.0038, p = 0.031).

Conclusions: Early in HIV infection, increases of Cho/Cr and MI/Cr in treatment-naive participants suggest progressive inflammation and gliosis in the frontal white matter and parietal gray matter, which is attenuated after initiation of ART. Elevated baseline Glu/Cr in basal ganglia may signal excitotoxicity; its subsequent stabilization and downward trajectory with ART may lend further support for early ART initiation.

Publication types

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

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / pharmacology*
  • Cerebrum / drug effects
  • Cerebrum / metabolism*
  • Chronic Disease
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy / instrumentation
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged


  • Anti-Retroviral Agents