Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Serena Spudich

Subject Area(s)

Medicine

Abstract

CEREBRAL METABOLITE CHANGES PRIOR TO AND AFTER ANTIRETROVIRAL THERAPY IN PRIMARY HIV INFECTION.

Andrew C. Young1, Constantin T. Yiannoutsos2, Manu Hegde3, Evelyn Lee3, Julia Peterson3, Rudy Walter3, Richard W. Price3, Dieter J. Meyherhoff3, and Serena Spudich1.

Department of Neurology, Yale University, School of Medicine, New Haven, CT

Indiana University, Indianapolis, IN

University of California, San Francisco (UCSF), San Francisco, CA

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).

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.

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 = 20.0038, p = 0.031).

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.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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