White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

Li, J.; Wu, Guangyao; Wen, Zhi; Zhang, J.; Lei, Hao; Gui, Xien; Lin, Fuchun Joseph

doi:10.3174/ajnr.a4417

Cited by 21 publications

(19 citation statements)

References 36 publications

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“…In contrast to other studies reporting FA reductions in the corpus callosum (CC) in children and youths on ART (Hoare et al, 2015 ; Li et al, 2015 ), we continue, as at 5 years (Ackermann et al, 2016 ), to find no evidence of microstructural CC damage at age 7 years in these children who all initiated ART by 18 months of age. The lack of HIV associated WM damage in the CC suggests that early treatment is neuroprotective to the CC.…”

Section: Discussioncontrasting

confidence: 99%

“…In contrast to our findings, Li et al ( 2015 ) found that longer ART duration and earlier age of treatment initiation was associated with lower frontal FA in infected youths. In their study, children initiated treatment when clinically indicated.…”

Section: Discussioncontrasting

confidence: 99%

“…Notably, we observe increasing damage in frontal WM (viz. ATR) in our children from 5 to 7 years, which overlaps with the time when children in (Li et al, 2015 ) start to initiate ART (age of ART initiation: 50–190 months). These findings suggest that frontal WM may be more vulnerable to ongoing HIV infection over this period of development, or that an early insult negatively impacts later development.…”

Section: Discussionmentioning

confidence: 52%

“…While we found HIV-related RD increases in the SCR, Hoare et al ( 2015 ) reported RD increases in the anterior corona radiate in children aged 6–16 years on ART. In infected children aged 13–17 years on ART, Li et al ( 2015 ) found lower FA in the superior and posterior corona radiata, frontal and parietal WM, pre-/postcentral gyrus, and superior longitudinal fasciculus (SLF), all due to RD increases.…”

Section: Discussionmentioning

confidence: 99%

“…DTI studies in HIV infected (HIV+) children and adolescents on ART have found lower whole brain (Uban et al, 2015 ) and regional FA, including the corpus callosum (CC), fornix, corona radiata, frontal and parietal WM, pre-/postcentral gyrus, and superior longitudinal fasciculus (Hoare et al, 2015 ; Li et al, 2015 ). Reductions in FA were attributed to RD increases, suggesting effects of HIV on myelination.…”

Section: Introductionmentioning

confidence: 99%

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White Matter Abnormalities in Children with HIV Infection and Exposure

et al. 2017

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Background: Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART.Methods: We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and 46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7-year-old children. This is a follow up of a cohort studied at 5 years, where we previously reported lower fractional anisotropy (FA) in corticospinal tract (CST) and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in HIV+ children compared to uninfected controls. In addition, we also found a difference in FA related to age at which ART was initiated.Results: At 7 years, we found two regions in the left IFOF and left ILF with lower FA in HIV+ children compared to controls. Higher MD was observed in a similar region in the IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the right forceps minor. Unlike at 5 years, we found no impact on WM of ART initiation. In HEU children, we found a cluster in the right posterior corona radiata with higher FA compared to HU children, while bilateral regions in the CST demonstrated reduced MD.Conclusions: At age 7, despite early ART and viral load (VL) suppression, we continue to observe differences in WM integrity. WM damage observed at age 5 years persists, and new damage is evident. The continued observation of regions with lower FA and higher MD in HIV+ children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the CST tract suggesting that perinatal HIV/ART exposure has a long-term impact on WM development.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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White Matter Abnormalities in Children with HIV Infection and Exposure

et al. 2017

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Multimodal magnetic resonance neuroimaging measures characteristic of early cART‐treated pediatric HIV: A feature selection approach

Khobo

Jankiewicz

Holmes

et al. 2022

Human Brain Mapping

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Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV‐related brain alterations can be investigated separately using proton magnetic resonance spectroscopy ( 1 H‐MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic‐net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and 1 H‐MRS in basal measures to sMRI volumes produced the highest classification performance . The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART‐treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV.

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Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV

et al. 2019

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Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. 46 adolescents who initiated ART during the first 2 years of life (<2yrs), and 79 adolescents who initiated ART after 2 years of age (>2yrs), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD) and radial diffusion (RD) in a region of interest analysis.Neurocognitive performance was similar between adolescents who initiated ART <2yrs or >2yrs. There was a trend towards attention (p=.07) and working memory (p=.05) being poorer in the group who initiated ART >2yrs. FA was lower in the >2yrs group in the superior corona radiata (p=.03), and the external capsule (p=.04). MD was higher in the >2yrs group in the cerebral peduncle (p=.02), the superior corona radiata (p=.01) and the superior fronto-occipital fasciculus (p=.03). RD was higher in the >2yrs group in the superior corona radiata (p=.02), the cerebral peduncle (p=.01) and the superior fronto-occipital fasciculus (p=.01). However the higher AD in the >2yrs group in the superior corona radiata was not in the expected direction (p=.01). Initiation

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White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

Cited by 21 publications

References 36 publications

White Matter Abnormalities in Children with HIV Infection and Exposure

White Matter Abnormalities in Children with HIV Infection and Exposure

Multimodal magnetic resonance neuroimaging measures characteristic of early cART‐treated pediatric HIV: A feature selection approach

Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV

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