ArticlePloS one2017
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Neonatal HIV prophylaxis is associated with accelerated presentation and clinical progression of MPV17-related mitochondrial neurohepatopathy.BMC pediatrics · 2026Article
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- Maternal HIV Infection and Antiretroviral Therapy in Pregnancy: Implications for Vertical Transmission, Fetal Safety, and Long-Term Infant Outcomes.Pathogens (Basel, Switzerland) · 2025Review
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- Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications.Frontiers in immunology · 2023Review
- Genome-scale metabolic models for natural and long-term drug-induced viral control in HIV infection.Life science alliance · 2022Article
- Review
- Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages.Antimicrobial agents and chemotherapy · 2022Article
- Effects of nutritional supplementation on glucose metabolism and insulin function among people with HIV initiating ART.BMC nutrition · 2021Article
- Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.Children (Basel, Switzerland) · 2021Article
- The struggle of a good friend getting old: cellular senescence in viral responses and therapy.EMBO reports · 2021Review
- Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1.Journal of clinical medicine · 2020Article
- Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.Frontiers in genetics · 2020Article
- Kidney Disease in HIV Infection.Journal of clinical medicine · 2019Review
- KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.Nature communications · 2019Article
- HIV infection and latency induce a unique metabolic signature in human macrophages.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of first generation NRTIs, which are rarely discussed in the literature, include inhibition of oxygen consumption, decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure.
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