Andrew C Young1, Constantin T Yiannoutsos1, Manu Hegde1, Evelyn Lee1, Julia Peterson1, Rudy Walter1, Richard W Price1, Dieter J Meyerhoff1, Serena Spudich2. 1. 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. 2. 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.
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.
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: S Lindbäck; A C Karlsson; J Mittler; A Blaxhult; M Carlsson; G Briheim; A Sönnerborg; H Gaines Journal: AIDS Date: 2000-10-20 Impact factor: 4.177
Authors: L E Davis; B L Hjelle; V E Miller; D L Palmer; A L Llewellyn; T L Merlin; S A Young; R G Mills; W Wachsman; C A Wiley Journal: Neurology Date: 1992-09 Impact factor: 9.910
Authors: B M Ances; D Sisti; F Vaida; C L Liang; O Leontiev; J E Perthen; R B Buxton; D Benson; D M Smith; S J Little; D D Richman; D J Moore; R J Ellis Journal: Neurology Date: 2009-09-01 Impact factor: 9.910
Authors: Eva-Maria Ratai; Sarah J Pilkenton; Jane B Greco; Margaret R Lentz; Jeffrey P Bombardier; Katherine W Turk; Julian He; Chan-Gyu Joo; Vallent Lee; Susan Westmoreland; Elkan Halpern; Andrew A Lackner; R Gilberto González Journal: BMC Neurosci Date: 2009-06-22 Impact factor: 3.288
Authors: Robert A Fuller; Susan V Westmoreland; Eva Ratai; Jane B Greco; John P Kim; Margaret R Lentz; Julian He; Prabhat K Sehgal; Eliezer Masliah; Elkan Halpern; Andrew A Lackner; R Gilberto González Journal: BMC Neurosci Date: 2004-03-05 Impact factor: 3.288