Dolutegravir-induced growth and lifespan effects in Caenorhabditis elegans

BMC Pharmacol Toxicol. 2023 Dec 7;24(1):74. doi: 10.1186/s40360-023-00715-5.

Abstract

Background: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders.

Methods: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan.

Results: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction.

Conclusions: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.

Keywords: Caenorhabditis Elegans; Dolutegravir (DTG); Lifespan; People living with HIV (PLWH); Reactive oxidative species (ROS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Drug-Related Side Effects and Adverse Reactions*
  • HIV Infections* / drug therapy
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase Inhibitors* / therapeutic use
  • Humans
  • Longevity
  • Reactive Oxygen Species

Substances

  • dolutegravir
  • HIV Integrase Inhibitors
  • Reactive Oxygen Species