Modelling Hepatotoxicity of Antiretroviral Therapy in the Liver during HIV Monoinfection

Abstract

Liver related complications are currently the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. In HIV monoinfected individuals on therapy, liver injury has been associated with the use of antiretroviral agents as most of them exhibit some degree of toxicity. In this study we proposed a mathematical model with the aim of investigating hepatotoxicity of combinational therapy of antiretroviral drugs. Therapy efficacy and toxicity were incorporated in the model as dose-response functions. With the parameter values used in the study, protease inhibitors-based regimens were found to be more toxic than nonnucleoside reverse transcriptase inhibitors-based regimens. In both regimens, the combination of stavudine and zidovudine was the most toxic baseline nucleoside reverse transcriptase inhibitors followed by didanosine with stavudine. However, the least toxic combinations were zidovudine and lamivudine followed by didanosine and lamivudine. The study proposed that, under the same second line regimens, the most toxic first line combination gives the highest viral load and vice versa.