Neuronal-Glia Markers by Magnetic Resonance Spectroscopy in HIV Before and After Combination Antiretroviral Therapy

J Acquir Immune Defic Syndr. 2016 Jan 1;71(1):24-30. doi: 10.1097/QAI.0000000000000779.

Abstract

Objective: Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV.

Methods: We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART.

Results: At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013).

Conclusions: cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Choline / metabolism
  • Cognition Disorders / etiology
  • Cognition Disorders / metabolism
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Neuroglia / metabolism*
  • Neurons / metabolism*

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Aspartic Acid
  • N-acetylaspartate
  • Choline