Abstract
Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.
Highlights
Indinavir is a potent protease inhibitor (PI) that has been used in adults and children in combination with nucleotide reverse transcriptase inhibitors to control the progression of human immunodeficiency virus (HIV) infection
The continuous use of antiretroviral therapy (ART) has been associated with a number of undesirable side effects that are associated with a range of metabolic complications and include dyslipidaemia, insulin resistance, overt diabetes mellitus and sudden death (Carr et al 1998, Anastos et al 2007, George et al 2010)
Considering the great similarities in plasma lipid composition and lipid metabolism between humans and hamsters, we postulated that hamsters (Mesocricetus auratus) might be an appropriate proxy for evaluation of the side effects of antiretroviral drugs (Alexaki et al 2004)
Summary
Indinavir is a potent protease inhibitor (PI) that has been used in adults and children in combination with nucleotide reverse transcriptase inhibitors to control the progression of human immunodeficiency virus (HIV) infection. At 6 mg/kg/day, we observed higher cholesterol and triacylglycerol (TG) levels at two months of treatment compared with levels in untreated animals in the high-fat diet group.
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