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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-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.
GLOSSARY
- ART=
- antiretroviral therapy;
- CHI=
- chronic HIV infection;
- Cho=
- choline-containing metabolites;
- Cr=
- creatine-containing metabolites;
- Glu=
- glutamate;
- 1H-MRS=
- proton magnetic resonance spectroscopy;
- IQR=
- interquartile range;
- MI=
- myo-inositol;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- MR=
- magnetic resonance;
- NAA=
- N-acetylaspartate;
- PHI=
- primary HIV infection;
- TCA=
- tricarboxylic acid;
- TE=
- echo time;
- VOI=
- volume of interest
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 1588
Supplemental data at Neurology.org
- Received January 5, 2014.
- Accepted in final form June 16, 2014.
- © 2014 American Academy of Neurology
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