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Efavirenz
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Indinavir
Maraviroc
Raltegravir
Zidovudine
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This patient who presents with hyperglycemia, hyperlipidemia, and inhibition of cytochrome P450 activity (as seen with an elevated INR in the setting of use of warfarin, a P450 substrate) after starting a new HIV medication was most likely started on a protease inhibitor such as indinavir. Protease inhibitors are an important class of medications that are used in the treatment of HIV. They are most commonly used as part of highly active antiretroviral therapy regimens. Important side effects of protease inhibitors include hyperglycemia, gastrointestinal upset, acute pancreatitis, and fat redistribution/lipodystrophy. Indinavir-specific side effects include nephropathy, kidney stones, hematuria, and thrombocytopenia. In addition, protease inhibitors have significant drug metabolism interactions because they are all CYP450 inhibitors that decrease the metabolism of other CYP450-dependant medications such as warfarin. Ismail et al. studied the mechanisms by which protease inhibitors lead to hyperglycemia and hyperlipidemia. They found that the insulin resistance induced by these medications is mediated by the NF-kB pathway. Incorrect Answers: Answer 1: Efavirenz is a non-nucleoside reverse transcriptase inhibitor that can also be used in the treatment of HIV; however, this drug is an inducer of the P450 system and is associated with the side effects of vivid dreams, confusion, and headaches. Answer 3: Maraviroc is a fusion inhibitor that can also be used in the treatment of HIV; however, this drug is associated with the side effect of hepatotoxicity and increased serum AST and ALT levels. Answer 4: Raltegravir is an integrase inhibitor that can also be used in the treatment of HIV; however, this drug is associated with the side effect of myalgias and increased serum creatine kinase levels. Answer 5: Zidovudine is a nucleoside reverse transcriptase inhibitor that can also be used in the treatment of HIV; however, this drug is associated with the side effect of pancreatitis. Bullet Summary: Protease inhibitors have the side effects of hyperlipidemia, hyperglycemia, and inhibition of cytochrome P450 activity.
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