Signs of Accentuated Brain Aging In Chronic HIV Infection under CART- MULTIVOXEL MR Spectroscopy Study

Jasmina Boban 1 Snezana Brkic 1,2 Dajana Lendak 1,2 Vojislava Bugarski Ignjatovic 1,3 Mladen Bjelan 1,4 Jelena Ostojic 5 Aleksandar Todorovic 1,4 Dusko Kozic 1,4
1Faculty of Medicine, University of Novi Sad, Serbia
2Clinic for Infectious Diseases, Clinical Center of Vojvodina, Serbia
3Clinic for Neurology, Clinical Center of Vojvodina, Serbia
4Center for Diagnostic Imaging, Oncology Institute of Vojvodina, Serbia
5Faculty of Health Sciences, Research Unit of Radiology, University of Southern Denmark, Denmark

PURPOSE: Recent neuroimaging studies reported progressive neurodegeneration and cerebral atrophy in chronic HIV patients, followed by decline in neurocognitive performance, compared to age-matched healthy subjects. The long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects with good peripheral viral suppression and continuous antiretroviral therapy (cART) are not widely studied yet. The aim of this study was to assess longitudinal changes in the neurometabolic profile in chronically-infected, HIV-positive subjects during a follow-up period of five years, using multi-voxel proton magnetic resonance spectroscopy (1H MRS).

MATERIAL & METHODS: We performed a longitudinal cohort studywith data collection from July 2011 to December 2016. Baseline neuroimaging was performed in 31 patients, and follow-up in 19 patients according to the inclusion criteria. A total of 19 neurologically asymptomatic, aviremic, stable on cART, HIV-positive subjects, met the study criteria and were included in the analyses. Eleven of 19 subjects underwent synchronous follow-up neurocognitive assessment. Neurometabolic ratios were extracted with multi-voxel 1H MRS on 3T MR unit (Trio Tim, Siemens, Germany). Twelve voxels were analyzed in the prefrontal cortices, the anterior and posterior cingulate gyrus, the intraparietal sulci, and the frontal centrum semiovale white matter, to identify peaks of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. The Wilcoxon signed-rank-test for repeated measurements was used to test longitudinal differences in ratios and neurocognitive scores. Statistical significance was set at p≤0.004 significant, and 0.05>p>0.004 trending toward significance (Bonferroni correction was applied due to a small study sample).

RESULTS: A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three voxels. The increase in Cho/Cr reached statistical significance only in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels.

CONCLUSIONS: A progressive increase in NAA/Cr, followed by the better neurocognitive performance, may be an indicator of at least a partial functional recovery and brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Jasmina Boban
Jasmina Boban