Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

[1]  H. Tallan Studies on the distribution of N-acetyl-L-aspartic acid in brain. , 1957, The Journal of biological chemistry.

[2]  E. Halpern,et al.  In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain , 2009, BMC Neuroscience.

[3]  Igor D. Grachev,et al.  Chemical Heterogeneity of the Living Human Brain: A Proton MR Spectroscopy Study on the Effects of Sex, Age, and Brain Region , 2000, NeuroImage.

[4]  I. Wilkinson,et al.  A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS. , 1996, AIDS research and human retroviruses.

[5]  Linda Chang,et al.  Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. , 2007, The Journal of neuropsychiatry and clinical neurosciences.

[6]  L. Montagnier,et al.  Early viral replication in the brain of SIV-infected rhesus monkeys. , 1991, The American journal of pathology.

[7]  Eric S. Rosenberg,et al.  Alterations in brain metabolism during the first year of HIV infection , 2011, Journal of NeuroVirology.

[8]  Linda Chang,et al.  Regional patterns of brain metabolites in AIDS dementia complex , 2004, NeuroImage.

[9]  D. Leibfritz,et al.  Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. , 1993, Developmental neuroscience.

[10]  M. Harris-White,et al.  Thinking about HIV: the intersection of virus, neuroinflammation and cognitive dysfunction , 2010, Immunologic research.

[11]  Michael J. Taylor,et al.  Cerebral Metabolite Abnormalities in Human Immunodeficiency Virus Are Associated with Cortical and Subcortical Volumes , 2022 .

[12]  I. Grant,et al.  Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. , 2002, Archives of neurology.

[13]  M. Dichter,et al.  Human Immunodeficiency Virus (HIV)-Induced Neurotoxicity: Roles for the NMDA Receptor Subtypes , 2006, The Journal of Neuroscience.

[14]  Jerome H. Kim,et al.  Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection , 2012, PloS one.

[15]  Jintanat Ananworanich,et al.  Central nervous system viral invasion and inflammation during acute HIV infection. , 2012, The Journal of infectious diseases.

[16]  Herbert Budka,et al.  Neuropathology of Human Immunodeficiency Virus Infection , 1991, Brain pathology.

[17]  E. Rosenberg,et al.  Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection , 2009, Neurology.

[18]  J. Catalan,et al.  Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection , 1997, AIDS.

[19]  B. Ross,et al.  Evidence of reduced glutamate in the frontal lobe of HIV‐seropositive patients , 2009, NMR in biomedicine.

[20]  Francisco González-Scarano,et al.  The neuropathogenesis of AIDS , 2005, Nature Reviews Immunology.

[21]  G. Fein,et al.  N-acetylaspartate reductions measured by 1H MRSI in cognitively impaired HIV-seropositive individuals. , 1994, Magnetic resonance imaging.

[22]  Justin C McArthur,et al.  The prevalence and incidence of neurocognitive impairment in the HAART era , 2007, AIDS.

[23]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[24]  D P Auer,et al.  On the reliability of quantitative clinical magnetic resonance spectroscopy of the human brain , 1995, NMR in biomedicine.

[25]  L. Wald,et al.  Theory and application of array coils in MR spectroscopy , 1997, NMR in biomedicine.

[26]  H. Gendelman,et al.  Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages , 2001, Journal of Neuroimmunology.

[27]  S. Bluml,et al.  Magnetic resonance spectroscopy of the human brain , 2001, The Anatomical record.