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

Andrew C. Young, Constantin Yiannoutsos, Manu Hegde, Evelyn Lee, Julia Peterson, Rudy Walter, Richard W. Price, Dieter J. Meyerhoff, Serena Spudich

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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-containingmetabolites (Cho) weremeasured relative to creatine1 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 5 0.0012, p = 0.005) and MI/Cr (slope 5 0.0041, p = 0.005) in frontal white matter as well as increases in MI/Cr (slope 5 0.0041, p <0.001) and NAA/Cr (slope 5 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 5 -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.

Original languageEnglish (US)
Pages (from-to)1592-1600
Number of pages9
JournalNeurology
Volume83
Issue number18
StatePublished - Oct 1 2014

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HIV Infections
Inositol
Choline
Basal Ganglia
Glutamic Acid
Secondary Prevention
Therapeutics
Gliosis
Phosphocreatine
Gyrus Cinguli
Magnetic Resonance Spectroscopy
HIV
Inflammation
Brain
White Matter
Gray Matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Young, A. C., Yiannoutsos, C., Hegde, M., Lee, E., Peterson, J., Walter, R., ... Spudich, S. (2014). Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology, 83(18), 1592-1600.

Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. / Young, Andrew C.; Yiannoutsos, Constantin; Hegde, Manu; Lee, Evelyn; Peterson, Julia; Walter, Rudy; Price, Richard W.; Meyerhoff, Dieter J.; Spudich, Serena.

In: Neurology, Vol. 83, No. 18, 01.10.2014, p. 1592-1600.

Research output: Contribution to journalArticle

Young, AC, Yiannoutsos, C, Hegde, M, Lee, E, Peterson, J, Walter, R, Price, RW, Meyerhoff, DJ & Spudich, S 2014, 'Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection', Neurology, vol. 83, no. 18, pp. 1592-1600.
Young AC, Yiannoutsos C, Hegde M, Lee E, Peterson J, Walter R et al. Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology. 2014 Oct 1;83(18):1592-1600.
Young, Andrew C. ; Yiannoutsos, Constantin ; Hegde, Manu ; Lee, Evelyn ; Peterson, Julia ; Walter, Rudy ; Price, Richard W. ; Meyerhoff, Dieter J. ; Spudich, Serena. / Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. In: Neurology. 2014 ; Vol. 83, No. 18. pp. 1592-1600.
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abstract = "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-containingmetabolites (Cho) weremeasured relative to creatine1 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 5 0.0012, p = 0.005) and MI/Cr (slope 5 0.0041, p = 0.005) in frontal white matter as well as increases in MI/Cr (slope 5 0.0041, p <0.001) and NAA/Cr (slope 5 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 5 -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.",
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AU - Peterson, Julia

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AB - 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-containingmetabolites (Cho) weremeasured relative to creatine1 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 5 0.0012, p = 0.005) and MI/Cr (slope 5 0.0041, p = 0.005) in frontal white matter as well as increases in MI/Cr (slope 5 0.0041, p <0.001) and NAA/Cr (slope 5 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 5 -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.

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