Efficacy of antiretroviral compounds against Toxoplasma gondii in vitro

Int J Antimicrob Agents. 2019 Dec;54(6):814-819. doi: 10.1016/j.ijantimicag.2019.08.023. Epub 2019 Aug 31.

Abstract

The obligate intracellular parasite Toxoplasma gondii can infect nearly all warm-blooded animals, including humans. Although infection with this parasite is generally benign, severe illness may occur in infected individuals if their immunity becomes less competent, such as in human immunodeficiency virus (HIV)-infected patients. In this study, the inhibitory activity of 44 commonly used antiretroviral compounds was determined against T. gondii in vitro. Of the 44 tested antiretroviral compounds, 14 showed potency against T. gondii at IC50 concentrations (concentration inhibiting T. gondii tachyzoite growth by 50%) ranging from 1.18 ± 2.21 µM (nelfinavir) to 18.89 ± 1.87 µM (trovirdine). Of the 14 potent antiretroviral compounds, 7 are HIV-1 protease inhibitors. This study also investigated whether co-administration of these 14 antiretroviral compounds interferes with the anti-T. gondii activity of existing anti-T. gondii drugs, namely sulfadiazine and pyrimethamine. The results showed no significant interaction between any of the 14 tested antiretroviral compounds and pyrimethamine or sulfadiazine. These results warrant investigation of whether administration of the lead antiretroviral drugs with highly potent anti-T. gondii activity to HIV patients may help to limit the occurrence of toxoplasmic encephalitis.

Keywords: AIDS; Antiretroviral compounds; Cerebral toxoplasmosis; Drug repurposing; HIV; Toxoplasma gondii.

MeSH terms

  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / pharmacology*
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / pharmacology
  • Cells, Cultured
  • Drug Interactions
  • Fibroblasts / drug effects
  • Humans
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / pharmacology
  • Sulfadiazine / administration & dosage
  • Sulfadiazine / pharmacology
  • Toxoplasma / drug effects*

Substances

  • Anti-Retroviral Agents
  • Antiprotozoal Agents
  • Sulfadiazine
  • Pyrimethamine