ArticleAIDS (London, England)2019
The antagonism of folate receptor by dolutegravir: developmental toxicity reduction by supplemental folic acid.
Article in AIDS (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Risk of Congenital Anomalies with Dolutegravir-Based Anti-retroviral Regimens: A Systematic Review and Meta-analysis.Clinical drug investigation · 2024Pooled it
- Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants.The Journal of infectious diseases · 2024Trial
- 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
- Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa.AIDS (London, England) · 2021Trial
- TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Morphological Variants and Factors Associated With Neural Tube Defects at a Regional Referral Hospital.Health science reports · 2026Article
- Dolutegravir developmental toxicity is mitigated by magnesium and folate in zebrafish embryos.Disease models & mechanisms · 2026Article
- CombinedActa biochimica et biophysica Sinica · 2025Article
- Fetal Defects in Mice Treated With Integrase Strand Transfer Inhibitors: Comparison of Dolutegravir, Raltegravir, Bictegravir, and Cabotegravir.The Journal of infectious diseases · 2025Article
- Post-marketing safety concerns with dolutegravir: a pharmacovigilance study based on the FDA adverse event reporting system database.Frontiers in pharmacology · 2025Article
- CEST MRI detects antiretroviral drug toxicities in the developing mouse brain.Frontiers in pharmacology · 2025Article
- Obstetric and newborn outcomes of mothers with and without HIV infection in Anaka general hospital in Northern Uganda.PloS one · 2025Article
- Biomarkers of the main nutritional components in purple rice during five successive grain filling stages.Food chemistry: X · 2024Article
- Combination of compound screening with an animal model identifies pentamidine to prevent Chlamydia trachomatis infection.Cell reports. Medicine · 2024Article
- RosetteArraybioRxiv : the preprint server for biology · 2024Article
- 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
- Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical 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
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMaternal folate (vitamin B9) status is the largest known modifier of neural tube defect risk, so we evaluated folate-related mechanisms of action for dolutegravir (DTG) developmental toxicity.
designFolate receptor 1 (FOLR1) was examined as a target for DTG developmental toxicity using protein and cellular interaction studies and an animal model.
methodsFOLR1 competitive binding studies were used to test DTG for FOLR1 antagonism. Human placenta cell line studies were used to test interactions with DTG, folate, and cations. Zebrafish were selected as an animal model to examine DTG-induced developmental toxicity and rescue strategies.
resultsFOLR1 binding studies indicate DTG is a noncompetitive FOLR1 antagonist at therapeutic concentrations. In-vitro testing indicates calcium (2 mmol/l) increases FOLR1-folate interactions and alters DTG-FOLR1-folate interactions and cytotoxicity. DTG does not inhibit downstream folate metabolism by dihydrofolate reductase. Early embryonic exposure to DTG is developmentally toxic in zebrafish, and supplemental folic acid can mitigate DTG developmental toxicity.
conclusionFolates and FOLR1 are established modifiers of risk for neural tube defects, and binding data indicates DTG is a partial antagonist of FOLR1. Supplemental folate can ameliorate increased developmental toxicity due to DTG in zebrafish. The results from these studies are expected to inform and guide future animal models and clinical studies of DTG-based antiretroviral therapy in women of childbearing age.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.