ArticleThe Journal of infectious diseases2022
Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models.
Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial.Journal of the International AIDS Society · 2023Trial
- Perinatal and early infant outcomes after first-versus second-generation integrase strand transfer inhibitor use in pregnancy.HIV medicine · 2026Article
- Fetal Defects in Mice Treated With Integrase Strand Transfer Inhibitors: Comparison of Dolutegravir, Raltegravir, Bictegravir, and Cabotegravir.The Journal of infectious diseases · 2025Article
- Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos.International journal of molecular sciences · 2024Article
- Dolutegravir induces FOLR1 expression during brain organoid development.Frontiers in molecular neuroscience · 2024Article
- Metabolic implications and safety of dolutegravir use in pregnancy.The lancet. HIV · 2023Review
- Cabotegravir Exposure of Zebrafish (International journal of molecular sciences · 2023Article
- Safety surveillance for PrEP in pregnant and breastfeeding women.Frontiers in reproductive health · 2023Review
- Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEach year, approximately 1.1 million children are exposed in utero to human immunodeficiency virus antiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube defect signal in infants exposed to the integrase strand transfer inhibitor (InSTI) dolutegravir from conception, suggesting that exposure during early fetal development may be detrimental.
methodsThe effects of InSTIs on 2 human embryonic stem cell (hESC) lines were characterized with respect to markers of pluripotency, early differentiation, and cellular health. In addition, fetal resorptions after exposure to InSTIs from conception were analyzed in pregnant mice.
resultsAt subtherapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased hESC counts and pluripotency and induced dysregulation of genes involved in early differentiation. At therapeutic concentrations, bictegravir induced substantial hESC death and fetal resorptions. It is notable that first-generation InSTI raltegravir did not induce any hESC toxicity or differentiation, at any concentration tested.
conclusionsExposure to some InSTIs, even at subtherapeutic concentrations, can induce adverse effects in hESCs and pregnant mice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of InSTIs on embryonic development, as well as their long-term safety after in utero exposure.
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Registered trials
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