Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study

Hof, Malon Van den; Jellema, Pien E J; Haar, Anne Marleen ter; Scherpbier, Henriëtte J.; Schrantee, Anouk; Kaiser, Antonia; Caan, Matthan W.A.; Majoie, Charles B. L. M.; Reiss, Peter; Wit, Ferdinand W. N. M.; Mutsaerts, Henk‐Jan

doi:10.1097/qad.0000000000002873

Cited by 8 publications

(22 citation statements)

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“…We found no association between WMH and Lp(a). The low absolute volume of WMH in our participants could have hampered the detection of this association [ 26 ]. We also found no association between white matter microstructure and Lp(a).…”

Section: Discussionmentioning

confidence: 99%

“…We also found no association between white matter microstructure and Lp(a). We assessed this association as previous studies reported mixed results and suggested that PHIV children possibly have a higher prevalence of white matter microstructure damage compared to matched controls [ 26 , 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…White matter hyperintensities (WMH) were previously determined by processing fluid attenuated inversion recovery (FLAIR) scans by means of a semi-automatic segmentation technique. One investigator (MvdH) manually segmented MRI under supervision of an experienced neuroradiologist using ITK-SNAP version 3.4.0 (Philadelphia, PA, USA and Salt Lake City, UT, USA): a segmentation software tool [ 25 , 26 ]. We also investigated associations with the following MRI parameters: Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD).…”

Section: Methodsmentioning

confidence: 99%

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Longitudinal Assessment of Lipoprotein(a) Levels in Perinatally HIV-Infected Children and Adolescents

Genderen

Hof

Boer

et al. 2021

Viruses

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HIV is an independent risk factor of cardiovascular disease (CVD); therefore, perinatally HIV-infected (PHIV) children potentially have a greater CVD risk at older age. Lipoprotein(a) (Lp(a)) is an established risk factor for CVD in the general population. To evaluate a potential increased CVD risk for PHIV children, we determined their lipid profiles including Lp(a). In the first substudy, we assessed the lipid profiles of 36 PHIV children visiting the outpatient clinic in Amsterdam between 2012 and 2020. In the second substudy, we enrolled 21 PHIV adolescents and 23 controls matched for age, sex and ethnic background on two occasions with a mean follow-up time of 4.6 years. We assessed trends of lipid profiles and their determinants, including patient and disease characteristics, using mixed models. In the first substudy, the majority of PHIV children were Black (92%) with a median age of 8.0y (5.7–10.8) at first assessment. Persistent elevated Lp(a) levels were present in 21/36 (58%) children (median: 374 mg/L (209–747); cut off = 300). In the second substudy, the median age of PHIV adolescents was 17.5y (15.5–20.7) and of matched controls 16.4y (15.8–19.5) at the second assessment. We found comparable lipid profiles between groups. In both studies, increases in LDL-cholesterol and total cholesterol were associated with higher Lp(a) levels. A majority of PHIV children and adolescents exhibited elevated Lp(a) levels, probably associated with ethnic background. Nonetheless, these elevated Lp(a) levels may additionally contribute to an increased CVD risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Longitudinal Assessment of Lipoprotein(a) Levels in Perinatally HIV-Infected Children and Adolescents

Genderen

Hof

Boer

et al. 2021

Viruses

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“…Although there were group differences in the pallidum at baseline, these attenuated over one year and group effects were considered minor by the authors; however, within the group with PHIV intriguing associations of CD4 count with pallidum shape and volume were observed. Similarly, findings from the Dutch NOVICE cohort suggest comparable maturational processes during later adolescence [75]. Longitudinal structural MRI and diffusion tensor imaging (DTI) were performed over 4.6 years for 20 youth with and 23 without HIV (mean age 18 and 17, respectively, at the follow-up visit).…”

Section: Selected Recent Neuroimaging Studies Among Adolescents and Y...mentioning

confidence: 96%

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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“…16 Although evidence suggests that children and adolescents with PHIV manifest subtle brain alterations compared with healthy controls, these studies did not match for, or report differences in, early-life characteristics, such as nutrition history or adoption status. [8][9][10]14,16 These factors are important because brain maturation is at a critical stage in early life 17 and adoption has been associated with malnutrition and neglect, 18 which, in turn, have been associated with altered brain development. 19,20 In the Netherlands, the majority of adolescents with PHIV have been adopted.…”

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Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls

et al. 2022

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Background and ObjectivesDespite effective combination antiretroviral therapy (cART), adolescents with perinatally acquired HIV (PHIV) exhibit cognitive impairment, of which structural changes could be the underlying pathophysiological mechanism. Prior MRI studies found lower brain volumes, more white matter (WM) hyperintensities (WMH) volume, lower WM integrity, and differences in cerebral blood flow (CBF). However, these findings may be confounded by adoption status, as the large portion PHIV adolescents have been adopted. Adoption has been associated with malnutrition and neglect which in turn may have affected brain development. We investigated the long-term effects of PHIV on the brain, while minimizing the confounding effect of adoption status.MethodsWe determined whole brain gray matter (GM) and WM volume with 3D T1-weighted scans; total WMH volume with fluid-attenuated inversion recovery (FLAIR); CBF in the following regions of interest (ROIs): WM, GM and subcortical GM with arterial spin labeling (ASL); and whole brain WM microstructural markers: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) with diffusion tensor imaging (DTI) in cART treated PHIV adolescents visiting our outpatient clinic in Amsterdam and controls matched for age, sex, ethnic origin, socio-economic status, and adoption status. We assessed differences in neuroimaging parameters between PHIV adolescents and controls using linear regression models adjusted for age and sex and applied multiple comparisons correction.Results35 PHIV adolescents and 38 controls were included with a median age (years) of 14.9 (IQR: 10.7-18.5) and 15.6 (IQR:11.1-17.6), respectively with a similar rate of adoption. We found a lower overall FA (beta = -0.012; p<0.014, -2.4%), higher MD (beta = 0.014, p = 0.014, 1.3%) and higher RD (beta = 0.02, p = 0.014, 3.3%) in PHIV adolescents vs. adoption-matched controls, but no differences in AD. We found comparable GM, WM and WMH volume, and CBF in ROIs between PHIV adolescents and controls. We did not find an association between cognitive profiles and WM microstructural markers in PHIV adolescents.DiscussionIrrespective of adoption status, PHIV adolescents exhibited subtle lower WM integrity. Our findings may point towards early-acquired WM microstructural alterations associated with HIV.

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Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study

Abstract: Supplemental Digital Content is available in the text

Cited by 8 publications

References 23 publications

Longitudinal Assessment of Lipoprotein(a) Levels in Perinatally HIV-Infected Children and Adolescents

Longitudinal Assessment of Lipoprotein(a) Levels in Perinatally HIV-Infected Children and Adolescents

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

Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls

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