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Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

  • Diagnostic Neuroradiology
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Abstract

Introduction

Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy (1H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART.

Methods

Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent 1H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed.

Results

Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014).

Conclusions

Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects.

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Acknowledgments

AW and SDT-R are grateful for support from the NIHR Biomedical Research Centre funding scheme at Imperial College Healthcare NHS Trust, London, UK, for infrastructure funding support. The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Government Department of Health & Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales. The ALTAIR study was funded with a research grant from Gilead Sciences, Foster City, CA, USA.

Conflict of interest

AW has received honoraria or research grants, or has been a consultant or investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Roche and Pfizer.

PL has been an investigator in clinical trials sponsored by Abbott, Bristol-Myers Squibb, Pfizer and Merck Sharp and Dohme, served on advisory boards of Abbott, Pfizer, Janssen-Cilag, Merck Sharp and Dohme and had been nominated by the Queen Elizabeth Hospital and local professional societies to attend conferences through grants from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme, Roche, IDS, Bayer Schering and Merck Serono.

JG has received honoraria, consultancies and research grants from (or has been an investigator in clinical trials sponsored by) Abbott, Bristol-Myers Squibb, Thera, Pfizer, Gilead Sciences, GlaxoSmithKline and Merck Sharp and Dohme.

SE has received honoraria, consultancies and research grants from (or has been an investigator in clinical trials sponsored by) Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Chiron-Novartis, Gilead Sciences, GlaxoSmithKline, Merck Sharp and Dohme, Roche, Tibotec and Virax Immunotherapeutics.

DAC has received honoraria, consultancies and research grants from (or has been an investigator in clinical trials sponsored by) Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline and Merck Sharp and Dohme.

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Authors and Affiliations

  1. St. Mary’s Hospital, Imperial College London, Ground Floor, Clinical Trials, Winston Churchill Wing, Praed Street, London, W2 1NY, UK

    Alan Winston & Simon D. Taylor-Robinson

  2. HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand

    Chris Duncombe & Stephen J. Kerr

  3. Queen Elizabeth Hospital, Kowloon, Hong Kong, People’s Republic of China

    Patrick C. K. Li

  4. Calgary Regional Health Authority, Calgary, Canada

    John M. Gill

  5. National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia

    Stephen J. Kerr, Rebekah L. Puls, Sean Emery & David A. Cooper

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  1. Alan Winston
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Winston, A., Duncombe, C., Li, P.C.K. et al. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy. Neuroradiology 54, 1331–1339 (2012). https://doi.org/10.1007/s00234-012-1061-5

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