ArticleJournal of pharmacological and toxicological methods
High-content analysis and Kinetic Image Cytometry identify toxicity and epigenetic effects of HIV antiretrovirals on human iPSC-neurons and primary neural precursor cells.
Article in Journal of pharmacological and toxicological methods. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- HIV associated epigenetic trends and chronic diseases: insights into the hidden burden of chronic infection.Clinical epigenetics · 2026Review
- In-context adaptation of VLMs for few-shot cell detection in optical microscopy.Frontiers in artificial intelligence · 2026Article
- CEST MRI detects antiretroviral drug toxicities in the developing mouse brain.Frontiers in pharmacology · 2025Article
- Tracking induced pluripotent stem cell differentiation with a fluorescent genetically encoded epigenetic probe.Cellular and molecular life sciences : CMLS · 2024Article
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- Human iPSC-derived neurons reveal NMDAR-independent dysfunction following HIV-associated insults.Frontiers in molecular neuroscience · 2023Article
- Long-acting dolutegravir formulations prevent neurodevelopmental impairments in a mouse model.Frontiers in pharmacology · 2023Article
- HIV-1 Integrase Strand Transfer Inhibitors and Neurodevelopment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Studying Chromatin Epigenetics with Fluorescence Microscopy.International journal of molecular sciences · 2022Review
- HIV Latency in Myeloid Cells: Challenges for a Cure.Pathogens (Basel, Switzerland) · 2022Review
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
introductionDespite viral suppression due to combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) continue to affect half of people with HIV, suggesting that certain antiretrovirals (ARVs) may contribute to HAND.
methodsWe examined the effects of nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG) on viability, structure, and function of glutamatergic neurons (a subtype of CNS neuron involved in cognition) derived from human induced pluripotent stem cells (hiPSC-neurons), and primary human neural precursor cells (hNPCs), which are responsible for neurogenesis.
resultsUsing automated digital microscopy and image analysis (high content analysis, HCA), we found that DTG, EVG, and TDF decreased hiPSC-neuron viability, neurites, and synapses after 7 days of treatment. Analysis of hiPSC-neuron calcium activity using Kinetic Image Cytometry (KIC) demonstrated that DTG and EVG also decreased the frequency and magnitude of intracellular calcium transients. Longer ARV exposures and simultaneous exposure to multiple ARVs increased the magnitude of these neurotoxic effects. Using the Microscopic Imaging of Epigenetic Landscapes (MIEL) assay, we found that TDF decreased hNPC viability and changed the distribution of histone modifications that regulate chromatin packing, suggesting that TDF may reduce neuroprogenitor pools important for CNS development and maintenance of cognition in adults.
conclusionThis study establishes human preclinical assays that can screen potential ARVs for CNS toxicity to develop safer cART regimens and HAND therapeutics.
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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.