Covertly active and progressing neurochemical abnormalities in suppressed HIV infection

Lucette A Cysique; Lauriane Jugé; Thomas Gates; Michael Tobia; Kirsten Moffat; Bruce J Brew; Caroline Rae

doi:10.1212/NXI.0000000000000430

Covertly active and progressing neurochemical abnormalities in suppressed HIV infection

Neurol Neuroimmunol Neuroinflamm. 2018 Jan 3;5(1):e430. doi: 10.1212/NXI.0000000000000430. eCollection 2018 Jan.

Authors

Lucette A Cysique¹, Lauriane Jugé¹, Thomas Gates¹, Michael Tobia¹, Kirsten Moffat¹, Bruce J Brew¹, Caroline Rae¹

Affiliation

¹ School of Medical Sciences (L.A.C., L.J., M.T., C.R.), Faculty of Medicine, UNSW Australia, Sydney; Neuroscience Research Australia (L.A.C., L.J., C.R.), Randwick; Peter Duncan Neuroscience Research Unit (L.A.C., T.G., B.J.B.), St. Vincent's Applied Medical Research Center, Darlinghurst; and St. Vincent's Hospital Sydney (L.A.C., T.G., K.M., B.J.B.), Darlinghurst, New South Wales, Australia.

Abstract

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.