Comparison between first- and second-generation non-nucleoside reverse transcriptase inhibitors effect on beta cell function and viability

Abstract

Abstract: Background and aim: The development of effective antiviral therapy has remarkably increased the lifespan of HIV-treated patients; however, the use of highly active antiretroviral medications has been linked to increase diabetes incidence among Human immunodeficiency virus (HIV)-treated patients. 1st generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) like efavirenz have also been shown to have direct cellular damaging effects in hepatocytes, endothelial cells and others. Such toxicity if occurred in ß-cells may prone HIV type 2 diabetic patients to susceptibility to ß-cell failure and insulin dependency. The aim of this study is to determine the effect of both 1st and 2nd generation NNRTIs on ß-cell function and viability. Methodology: Rat insulinoma INS-1E cell line were exposed to efavirenz, rilpivirine and doravirine (1-30 µM) for 24 or 48 hours before measuring cell viability using MTT assay, ß-cell function by glucose stimulated insulin release, oxidative stress by NBT assay, antioxidant capacity by ABTS assay, apoptosis and CHOP expression by specific ELISAs. Statistical analysis was performed using ANOVA and p< 0.05 was considered the level of significance. Results: Exposure of INS-1E cells to efavirenz and rilpivirine but not doravirine caused a decrease in insulin secretion, impairment of cell viability, increase in cell apoptosis and increase in the expression of the ER stress marker (CHOP). These deleterious effects were associated with both an increase in intracellular oxidative stress and a decrease in cellular antioxidant capacity. Conclusion: Efavirenz and rilpivirine can directly damage ß-cells causing loss of its function and thus increase the risk of diabetic patients to become insulin dependent. Doravirine appears to be a better treatment option for HIV patients who are Type 2 diabetic.