Possible Metabolic Interactions between Antiretroviral Drugs and Antidiabetic Drugs: an Overview

The availability of potent combination antiretroviral regimens has resulted in a dramatic reduction in HIV-1 associated morbidity and mortality in the developed world. However, HIV infection and treatment has been associated with the development of insulin resistance, glucose intolerance and diabetes. Besides, there can be co-morbid situations of HIV infection and diabetes. Safe pharmacological treatment of these complications requires an understanding of the drug-drug interactions between antiretroviral drugs and the drugs used in the treatment of diabetes. Since formal studies of most of these interactions have not been performed, predictions must be based on our understanding of the metabolism of these agents. All HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors that have been approved by the Food and Drug Administration (FDA) are metabolized by the cytochrome P-450 enzyme system, primarily by the CYP3A4 isoform and each of these drugs may alter the metabolism of other antiretroviral and concomitantly administered drugs. In addition, protease inhibitors and nonnucleoside reverse transcriptase inhibitors are substrates, inducers and inhibitors of the cytochrome P-450 enzyme system. Sulphonylureas are metabolized by CYP2C9. Gliclazide, nateglinide, pioglitazone, troglitazone involves CYP3A4 metabolism also. Some drugs from each category are having mixed properties on cytochrome P-450 enzyme system. The concomitant administration of these drugs causes potentially significant drug interactions from induction or inhibition. Overall, well-designed drug-drug interaction studies at steady state are needed to determine whether antiretroviral drugs may be safely co-administered with the drugs used in the treatment of the diabetic complications of HIV infection.