State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, P.R. China.
Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
Int J Antimicrob Agents. 2019 Dec;54(6):814-819. doi: 10.1016/j.ijantimicag.2019.08.023. Epub 2019 Aug 31.
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 IC 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.
刚地弓形虫是一种专性细胞内寄生虫,可以感染几乎所有的温血动物,包括人类。虽然感染这种寄生虫通常是良性的,但如果感染者的免疫力下降,如感染人类免疫缺陷病毒(HIV)的患者,可能会出现严重疾病。在这项研究中,测定了 44 种常用抗逆转录病毒化合物对体外弓形虫的抑制活性。在 44 种测试的抗逆转录病毒化合物中,有 14 种化合物对 T. gondii 的 IC浓度(抑制 T. gondii 速殖子生长 50%的浓度)表现出活性,范围从 1.18 ± 2.21 µM(奈非那韦)到 18.89 ± 1.87 µM(替诺福韦)。在这 14 种有效抗逆转录病毒化合物中,有 7 种是 HIV-1 蛋白酶抑制剂。本研究还调查了这些 14 种抗逆转录病毒化合物与现有的抗弓形虫药物磺胺嘧啶和乙胺嘧啶联合使用是否会干扰其抗弓形虫活性。结果显示,这 14 种测试的抗逆转录病毒化合物与乙胺嘧啶或磺胺嘧啶之间没有显著的相互作用。这些结果表明,对于 HIV 患者,给予具有高度抗弓形虫活性的主导抗逆转录病毒药物可能有助于限制弓形体脑炎的发生,值得进一步研究。