Antiretroviral Therapy‐Induced Cerebellar Disorders: Efavirenz, Lamivudine, Tenofovir Disoproxil Fumarate; Which is Guilty?

Abstract

IntroductionCombination antiretroviral therapy (cART) has transformed the landscape of managing Human Immunodeficiency Virus (HIV) infection. However, there have been various reports on the deleterious activities of the therapy on patients' cerebellar function. Therefore, the aim of this study is to ascertain the effects of individual administration of tenofovir disoproxil fumarate, Lamivudine and efavirenz (ingredients of cART) on the cerebellum.Materials and MethodsForty adult Wistar rat were used for this study. They were divided into four groups according to the substances administered: distilled water, tenofovir disoproxil fumarate, lamivudine and efavirenz. After 35 days of administration, the animals underwent open field and beam walk tests. They were euthanized and the brain was prepared for oxidative stress assay, histological (Giemsa stain, Hematoxylin and Eosin stain) and immunohistochemical (GFAP and Dopamine) analysis. Ethical clearance protocol number: CMUL/HREC/03/17/113.ResultsThere was significant decrease in rearing, grooming, and line crossing in treatment groups most especially lamivudine group compared to control group. The latency, right and left hind limb slips increased significantly (p<0.01) in lamivudine group compared to control. There was a statistically significant decrease in the superoxide dismutase levels in the efavirenz group compared to control group (p<0.001). Tenofovir showed a significant increase in catalase level compared to the control group (p<0.001). Tenofovir, lamivudine and Efavirenz showed a significant increase in lipid peroxidation level compared to the control group. Histology analysis showed a degeneration/decrease in the granular and Purkinje cells in treatment groups compared to the control group. There was also a significant proliferation of astrocytes and a decrease in dopamine expression in Lamivudine groups compared to control.ConclusionThis study shows that tenofovir disoproxil fumarate and efavirenz cause various toxicities on the motor function of the cerebellum. However, Lamivudine is the major culprit in cART‐induced cerebellar disorders.Support or Funding InformationResearch reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW010134, through the Building Research and Innovation in Nigeria's Science (BRAINS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.