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Record W4413655718 · doi:10.1186/s12916-025-04332-3

Structural brain differences in school-aged children who are HIV-exposed uninfected

2025· article· en· W4413655718 on OpenAlexafffundabout
Eve A. Forster, Bilal Syed, Jennifer Bowes, J. Christopher Young, Cassandra Kapoor, Mark Head, Jason P. Lerch, Elka Miller, Jason Brophy, Ari Bitnun, Mary Lou Smith, Lena Serghides, Margot J. Taylor, John G. Sled

Bibliographic record

VenueBMC Medicine · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsWomen's College HospitalToronto General HospitalUniversity of TorontoUniversity Health NetworkChildren's Hospital of Eastern OntarioUniversity of OttawaHospital for Sick Children
FundersCanadian Institutes of Health ResearchCanada Research Chairs
KeywordsMedicineIn uteroBrain sizeWhite matterPopulationHuman immunodeficiency virus (HIV)Magnetic resonance imagingPhysiologyPediatricsPregnancyRadiologyImmunologyFetus

Abstract

fetched live from OpenAlex

Abstract Background Antiretroviral therapy (ART) has dramatically reduced perinatal HIV transmission, leading to a growing population of children who are HIV-exposed but uninfected (CHEU). While the neuroanatomic developmental impacts of in utero HIV and ART exposure have been studied in young children, long-term effects on school-aged children are poorly understood, prompting this investigation. Methods Fifty-eight CHEU and 38 children who are HIV-unexposed, uninfected (CHUU), 6–12 years old, were recruited through hospitals and community groups in Ontario, Canada. From T1-weighted magnetic resonance images, volume, cortical thickness, and gray-/white-matter tissue volume were extracted. Multiple linear regression models controlling for sex, age, household income, and total brain volume were fit to assess differences by in utero HIV exposure, with additional sex-stratified analyses to uncover sex-specific effects. Results Compared with CHUU, CHEU showed total brain volumes that were significantly smaller by 49.7cm 3 (95% CI [− 95.66, − 3.67]) and cortices thinner by 0.08 mm (95% CI [− 0.13, − 0.02]). In male CHEU, three regions displayed volumetric age-exposure interactions: the bilateral pars opercularis at 0.36 cm 3 /year (95% CI [0.10, 0.62]), left rolandic operculum at 0.22 cm 3 /year (95% CI [0.04, 0.39]) and left precentral gyrus at 0.71 cm 3 /year (95% CI [0.22, 1.21]), suggesting delayed maturation in those regions. Bilateral frontal lobe cortical thickness was reduced by 0.07 mm in CHEU (95% CI [− 0.14, − 0.006]), most pronounced in the left orbital middle frontal gyrus with a reduction of 0.20 mm among male CHEU (95% CI [− 0.32, − 0.07]). An age-exposure interaction of 0.06 cm 3 /year in bilateral amygdala volume (95% CI [− 0.11, − 0.01]) suggested reduced growth or altered developmental trajectory among CHEU, whereas male CHEU showed bilateral hippocampal volumes diminished by 0.21 cm 3 (95% CI [− 0.40, − 0.01]). Conclusions These findings suggest that in utero HIV and ART exposure have broad neuroanatomic developmental impacts, particularly in boys, with significant differences in brain regions critical for motor function, expressive language, memory, and emotion. These structural differences align with previously reported motor and language deficits and highlight the importance of early intervention and tailored support strategies for CHEU.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.023
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.275
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2025
Admission routes3
Has abstractyes

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