ArticlePloS one2020
In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Placenta models for HIV-1-ART-nicotine comorbidity research: advances and remaining challenges.Cell death discovery · 2026Review
- Impact of prenatal delta-9-tetrahydrocannabinol exposure on mouse brain development: a fetal-to-adulthood magnetic resonance imaging study.Molecular psychiatry · 2026Article
- Dynamic Telomere Length Response to Neurodevelopmental Arsenic Exposure: Insights into Transcriptional Regulation and Neuronal Morphogenesis.Environment & health (Washington, D.C.) · 2025Article
- Actinomycetospora lemnae sp. nov., A Novel Actinobacterium Isolated from Lemna aequinoctialis Able to Enhance Duckweed Growth.Current microbiology · 2024Article
- Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.Frontiers in molecular neuroscience · 2024Article
- In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.AIDS patient care and STDs · 2023Article
- The Parkinson's disease variant rs356182 regulates neuronal differentiation independently from alpha-synuclein.Human molecular genetics · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.
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