A Systematic Review of Magnetic Resonance Imaging Studies in Perinatally HIV-Infected Individuals

Martín-Bejarano, Manuela; Ruiz-Saez, Beatriz; Aragón, Ana Martínez de; Melero, Helena; Zamora, Berta; Malpica, Norberto; Ramos, José Tomás; González-Tomé, María Isabel

doi:10.24875/aidsrev.20000088

Cited by 3 publications

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“…This has allowed HIV infected women to carry pregnancies with greatly reduced risk of PHIV transmission, and for children who acquired HIV perinatally to grow into adulthood with improved life expectancy and quality of life without major chronic comorbidities. However, significant neurological and neurocognitive complications persist in the brains of PHIV children and young adults despite the use of ART (Uban et al, 2015;Hoare et al, 2018;Sarma et al, 2019Sarma et al, , 2021Thakur et al, 2019;Van den Hof et al, 2019;Martin-Bejarano et al, 2021;Ruiz-Saez et al, 2021;Nichols, 2022). Extensive clinical studies in adult HIV patients indicated that most antiretrovirals either have poor penetration across the blood-brain barrier (BBB) or are effectively removed from the brain parenchyma, reducing their efficacy in suppressing HIV viral replication (Mzingwane and Tiemessen, 2017;Osborne et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Most MRI-based neuroimaging studies on PHIV have focused on structural brain morphometry and microstructural alterations (Van den Hof et al, 2019;Martin-Bejarano et al, 2021;Nichols, 2022). Systematic reviews of brain imaging studies of PHIV mainly reported lower grey matter (GM) volumes and cortical thinning in PHIV subjects compared to healthy controls (Cohen et al, 2016;Lewis-de Los Angeles et al, 2017;Li J. et al, 2018;Nwosu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults

Salan

Willen²,

Cuadra³

et al. 2023

Front. Neurosci.

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Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults

Salan

Willen²,

Cuadra³

et al. 2023

Front. Neurosci.

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“…A number of recent reviews have summarized the literature on cognitive and neuroimaging findings among children with PHIV [5,[8][9][10][11][12][13][14][15]. In general, these reviews acknowledge that, despite decreases in severe neurological sequelae since the advent of cART for children, cognitive impairments continue to be a concern, particularly in the developing world where ART is less available, older antiretroviral medications with greater neurotoxicity are more commonly used, and HIV encephalopathy continues to occur [16].…”

Section: Introductionmentioning

confidence: 99%

Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update

Nichols

2022

Curr HIV/AIDS Rep

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Purpose of Review Perinatally acquired HIV infection (PHIV) can confer neurodevelopmental risk. As children with PHIV increasingly survive through adolescence and into adulthood, understanding its long-term central nervous system (CNS) impacts is critical for maximizing adult outcomes and quality of life. Recent Findings Recently published neurocognitive and neuroimaging findings show impacts on the CNS associated with early HIV disease progression that endure into adolescence and young adulthood. Although developmental trajectories in adolescence largely appear stable, further research on maturational processes is indicated. Summary Although early antiretroviral therapy in infancy appears to be protective, it is not universally available and current youth largely developed without its benefit. The neurocognitive effects of HIV and the multiple other risks to neurodevelopment experienced by youth with PHIV call for further longitudinal research and a multifaceted approach to prevention and intervention.

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Plasma Neurofilament Light Is Not Associated with Ongoing Neuroaxonal Injury or Cognitive Decline in Perinatally HIV Infected Adolescents: A Brief Report

Post

Genderen

Heijst

et al. 2022

Viruses

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Despite combination antiretroviral therapy (cART), adolescents with perinatally acquired human immunodeficiency virus (PHIV) exhibit cerebral injury and cognitive impairment. Plasma neurofilament light (pNfL) is a biomarker identified as a promising marker associated with neuroaxonal injury and cognitive impairment. To investigate whether cerebral injury in cART-treated PHIV adolescents is persistent, we longitudinally measured pNfL. We included 21 PHIV adolescents and 23 controls, matched for age, sex, ethnic origin and socio-economic status. We measured pNfL in both groups and CSF NfL in PHIV adolescents using a highly sensitive Single Molecule Array (Simoa) immunoassay. We compared pNfL between groups over time with a mean follow-up time of 4.6 years and assessed its association with MRI outcomes, cognitive function and HIV-related characteristics using linear mixed models. The median age was 17.5 years (15.5–20.7) and 16.4 years (15.8–19.6) at the second assessment for PHIV adolescents and controls, respectively. We found comparable pNfL (PHIV vs. controls) at the first (2.9 pg/mL (IQR 2.0–3.8) and 3.0 pg/mL (IQR 2.3–3.5), p = 0.499) and second assessment (3.3 pg/mL (IQR 2.5–4.1) and 3.0 pg/mL (IQR 2.5–3.7), p = 0.658) and observed no longitudinal change (coefficient; −0.19, 95% −0.5 to 0.1, p = 0.244). No significant associations were found between pNfL and HIV- or cART-related variables, MRI outcomes or cognitive function. We observed low CSF NfL concentrations at the baseline in PHIV adolescents (100.8 pg/mL, SD = 47.5). Our results suggest that there is no ongoing neuroaxonal injury in cART-treated PHIV adolescents and that the neuroaxonal injury is acquired in the past, emphasizing the importance of early cART to mitigate HIV-related neuroaxonal damage.

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A Systematic Review of Magnetic Resonance Imaging Studies in Perinatally HIV-Infected Individuals

Cited by 3 publications

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Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults

Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults

Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update

Plasma Neurofilament Light Is Not Associated with Ongoing Neuroaxonal Injury or Cognitive Decline in Perinatally HIV Infected Adolescents: A Brief Report

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