Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection

Boban, Jasmina; Kozić, Duško; Turkulov, Vesna; Lendak, Dajana; Bjelan, Mladen; Semnic, Marija; Brkić, Snežana

doi:10.3174/ajnr.a5160

Cited by 13 publications

(12 citation statements)

References 28 publications

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“…When comparing HIV-positive patients of different age groups with age-matched healthy subjects, the results of our study showed that NAA/Cr ratios were significantly decreased in chronically infected, virally suppressed HIV-positive subjects, compared to healthy controls. This has also been observed in previous spectrosopic studies ( Bairwa et al, 2016 ; Boban et al, 2017 ). In HIV-positive subjects, the presence of HIV infection was the strongest contributor to this decline, followed by age.…”

Section: Discussionsupporting

confidence: 90%

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study

Boban

Kozić

Brkić

et al. 2018

Front. Aging Neurosci.

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Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS).Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20–29 years old), group 2 (30–39), group 3 (40–49) and group 4 (50–59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson’s correlation test. Statistical significance was set at p < 0.05.Results: The NAA/Cr ratios were decreased in the 20–29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50–59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations.Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART.Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.

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Section: Discussionsupporting

confidence: 90%

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study

Boban

Kozić

Brkić

et al. 2018

Front. Aging Neurosci.

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“…were the first to report a progressive reduction of the NAA level in HIV-positive subjects in a short follow-up period (three to eight months) 15 . Furthermore, based on later longitudinal studies, long-term control of both processes, neuroinflammation and consequent neurodegeneration, seemed to be suboptimal despite cART and good peripheral viral suppression 16 .…”

Section: Discussionmentioning

confidence: 99%

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study

Boban

Thurnher

Brkić

et al. 2019

Sci Rep

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There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and 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. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. 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. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of 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.

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“…Recent neuroimaging studies showed several important characteristics of brain injury in chronic HIV infection: global parenchymal reduction (loss of both gray and white matter), changes in the neurometabolic profile, and disturbances in neurotransmission (10,11). Studies based on magnetic resonance spectroscopy (MRS) showed ongoing inflammation and progressive neurodegeneration, even in virally suppressed, neurologically asymptomatic HIV-infected individuals with normal findings on conventional magnetic resonance imaging (MRI) (10,12). MRS is a non-invasive diagnostic modality that enables in vivo monitoring of subtle changes in the neurometabolic profile and has a potential role in the evaluation of cART efficacy in the CNS compartment.…”

Section: Introductionmentioning

confidence: 99%

CNS efficacy parameters of combination antiretroviral therapy in chronic HIV infection: A multi-voxel magnetic resonance spectroscopy study

et al. 2023

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This study aimed to determine the correlations of combination antiretroviral therapy (cART) efficacy parameters in the central nervous system (CNS) with a neurometabolic profile on magnetic resonance spectroscopy (MRS) in virally suppressed, neurologically asymptomatic HIV+ individuals. In total, 32 HIV+ individuals on stable cART with an average age of 41.97 ± 10.12 years and with available clinical data, CNS penetration effectiveness (CPE), and monocyte efficacy (ME) scores underwent multi-voxel MRS. The parameters of neuronal number/function (NAA/Cr), membrane turnover (Cho/Cr), and glial proliferation (mI/Cr) were analyzed in supratentorial white and gray matter. Correlations of CPE and ME with neurometabolic ratios were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. A strong positive correlation was observed between Cho/Cr and CPE in the left parietal subcortical white matter (r = 0.577, p = 0.001). A strong positive correlation between NAA/Cr and ME was obtained in the left (r = 0.521, p = 0.003) and the right (r = 0.494, p = 0.005) posterior cingulate. A strong negative correlation between ME and Cho/Cr ratios was observed in the right frontal deep white matter (r = −0.569, p = 0.001). Indices designed to assess cART efficacy in CNS failed to present significant correlations with the neurometabolic profile obtained using MRS. There is a need to define more potent non-invasive tools for neuroinflammation assessment given the prolonged life expectancy in the HIV+ population.

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Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection

Cited by 13 publications

References 28 publications

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study

CNS efficacy parameters of combination antiretroviral therapy in chronic HIV infection: A multi-voxel magnetic resonance spectroscopy study

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