Abstract
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.
Highlights
The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy, with age, gender, and educational-level-matched healthy subjects, using multivoxel magnetic-resonance spectroscopy (MRS)
The results of recent neuropsychological studies in HIV-related cognitive changes have raised the hypothesis of an accelerated brain aging process in chronic HIV infection (Simioni et al, 2010; Shouten et al, 2016)
Age-related decline has been thoroughly studied with diffusion tensor imaging (DTI), which showed decline in white matter tract integrity in healthy controls (Bennett et al, 2017)
Summary
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 multivoxel magnetic-resonance spectroscopy (MRS). There is an ongoing debate about whether a neurocognitive decline in chronic HIV infection represents an accentuation of physiological age-related changes, or an acceleration of otherwise normal brain aging (Sheppard et al, 2017). The results of recent neuropsychological studies in HIV-related cognitive changes have raised the hypothesis of an accelerated brain aging process in chronic HIV infection (Simioni et al, 2010; Shouten et al, 2016). In chronic HIV infection, atrophy of almost all brain regions has been reported, predominantly in the frontal and temporal regions, and more prominent than in matching healthy controls (Guha et al, 2016). DTI studies have failed to show any significant differences between healthy and HIV-positive subjects (Watson et al, 2017)
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