Abstract
This study comparatively investigated the toxicological effects of treatment with efavirenz, isoniazid and efavirenz-isoniazid (EFV- INH) combination on liver function parameters and histology of adult male albino rats. Animals used in this study were divided into five (5) groups A-E of sixteen (16) animals each. Animals in group A (placebo control) were treated with water while animals in group B (solvent control) were treated with arachis oil orally. Animals in groups C-E were treated orally with 15mg/kg of INH, 10mg/kg of EFV and a combination of INH- EFV for 2-8 weeks respectively. At the end of drug therapy, serum was extracted from centrifuged blood sample and evaluated for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and conjugated bilirubin. Animals were sacrificed and liver was harvested, weighed and evaluated for histopathological changes. Effects produced by co-treatment with EFV-INH on absolute liver weight, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, conjugated and total bilirubin were insignificant (p>0.05) when compared to effects produced by treatment with individual doses of EFV and INH. Histopathological evaluation of the liver of animals treated with EFV-INH combination showed vascular congestion, inflammation of parenchyma and hepatocytes degeneration. These results show that co- therapy with EFV-INH in patients with human immunodeficiency virus /tuberculosis co-infection may not be associated with synergistic hepatotoxicity.
Highlights
Human immunodeficiency virus (HIV) pandemic poses major threat to the socio-economic and psychological welfare of HIV infected people with decrease life expectancy
Absolute liver weight of animals treated with INH, EFV and INH–EFV combination did not differ significantly (p>0.05) from that of the control
Observations in this study show that co-therapy with INH–EFV in HIV/TB co-infection may not be associated with synergistic hepatotoxicity
Summary
Human immunodeficiency virus (HIV) pandemic poses major threat to the socio-economic and psychological welfare of HIV infected people with decrease life expectancy. The life expectancy of HIV-positive subjects has dramatically improved with the use of triple antiretroviral drug combinations [1]. Despite increase in life expectancy of HIV infected patients, toxicological effects of antiretroviral therapy have become a limiting cause of benefit in a substantial proportion of patients. Hepatotoxicity is one of the limiting toxicological effects that has been reported by many centers’ in developed world and is recognized as a major cause of morbidity and mortality in patients receiving antiretroviral treatment [2]. Efavirenz is one of the NNRTIs that have been implicated in hepatotoxicity in HIV-positive patients, especially where co-infection with hepatitis viruses is present [5,6,7]. Treatment with efavirenz containing antiretroviral regimens could be associated with fulminant liver failure which may lead to death [9]
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