PT - JOURNAL ARTICLE AU - Cysique, Lucette A. AU - Jugé, Lauriane AU - Gates, Thomas AU - Tobia, Michael AU - Moffat, Kirsten AU - Brew, Bruce J. AU - Rae, Caroline TI - Covertly active and progressing neurochemical abnormalities in suppressed HIV infection AID - 10.1212/NXI.0000000000000430 DP - 2018 Jan 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e430 VI - 5 IP - 1 4099 - http://nn.neurology.org/content/5/1/e430.short 4100 - http://nn.neurology.org/content/5/1/e430.full SO - Neurol Neuroimmunol Neuroinflamm2018 Jan 01; 5 AB - Objective To assess whether HIV-related brain injury is progressive in persons with suppressed HIV infection.Methods Seventy-three HIV+ virally suppressed men and 35 HIV− men, screened for psychiatric and alcohol/drug use disorders, underwent neuropsychological evaluation and proton magnetic resonance spectroscopy (1H-MRS) at baseline and after and 23 ± 5 months. 1H-MRS included brain regions known to be vulnerable to HIV and aging: frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate area (CA). Major brain metabolites such as creatine (Cr: marker of cellular energy), N-acetyl aspartate (NAA: marker of neuronal integrity), choline (marker of cellular membrane turnover), glutamate/glutamine (excitatory/inhibitory neurotransmitter), and myo-Inositol (mI: marker of neuroinflammation) were calculated with reference to water signal. Neurocognitive decline was corrected for practice effect and baseline HIV-associated neurocognitive disorder (HAND) status.Results Across the study period, 44% had intact cognition, 42% stable HAND (including the single case that improved), 10% progressing HAND, and 4% incident HAND. When analyzing the neurochemical data per neurocognitive trajectories, we found decreasing PCC Cr in all subgroups compared with controls (p < 0.002). In addition, relative to the HIV− group, stable HAND showed decreasing FWM Cr, incident HAND showed steep FWM Cr reduction, whereas progressing HAND had a sharply decreasing PCC NAA and reduced but stable CA NAA. When analyzing the neurochemical data at the group level (HIV+ vs HIV− groups), we found stable abnormal metabolite concentrations over the study period: decreased FWM and PCC Cr (both p < 0.001), decreased PCC NAA and CA NAA (both p < 0.05) and PCC mI increase (p < 0.05). HIV duration and historical HAND had modest effects on metabolite changes.Conclusions Our study reveals covertly active or progressing HIV-related brain injury in the majority of this virally suppressed cohort, reflecting ongoing neuropathogenic processes that are only partially worsened by historical HAND and HIV duration. Longer-term studies will be important for determining the prognosis of these slowly evolving neurochemical abnormalities.1H-MRS=proton magnetic resonance spectroscopy; ANI=asymptomatic neurocognitive impairment; CA=caudate area; cART=combination antiretroviral; Cr=creatine; Cho=choline; FWM=frontal white matter; GDS=Global Deficit Score; Glx=glutamate/glutamine; GM=gray matter; HAND=HIV-associated neurocognitive disorder; mI=myo-Inositol; MND=mild neurocognitive disorder; NAA=N-acetyl aspartate; PCC=posterior cingulate cortex