title: Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection.
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.
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Young
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Manu
authors.initials: M
authors.lastname: Hegde
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lee
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Rudy
authors.initials: R
authors.lastname: Walter
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco.
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Meyerhoff
authors.affiliation: From Yale University (A.C.Y., S.S.), New Haven, CT; Indiana University (C.T.Y.), Indianapolis; and the University of California (M.H., E.L., J.P., R.W., R.W.P., D.J.M.), San Francisco. serena.spudich@yale.edu.
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged
chemical_list: D044966:Anti-Retroviral Agents