Snapshot A 34-year-old man presents to the emergency room with acute epigastric pain. He denies any alcohol use. He is HIV-positive currently on highly active antiretroviral therapy. His past medical history is significant for a cholecystectomy 5 years ago without any complications. Laboratory evaluation reveals normal electrolytes, including calcium. A CT scan of his abdomen reveals acute pancreatitis. Upon careful review of his medications, 1 antiretroviral medication in particular increased this patient’s risk for acute pancreatitis. (Acute pancreatitis induced by a protease inhibitor) Introduction Drugs atazanavir darunavir fosamprenavir indinavir lopinavir nelfinavir ritonavir saquinavir tipranavir Mechanism of action inhibits HIV-1 protease (pol gene), which cleaves HIV mRNA prevents complete development of new viruses Mechanism of resistance usually requires multiple mutations in the pol gene Clinical use highly active antiretroviral therapy (HAART) second-line therapy for patients resistant to first-line therapies Adverse effects hyperglycemia gastrointestinal upset saquinavir acute pancreatitis fat redistribution/lipodystrophy Cushing-like syndrome with “buffalo hump” on the upper back indinavir-specific side effects nephropathy kidney stones hematuria thrombocytopenia interaction with rifampin (CYP450 inducer) rifampin decreases concentrations of protease inhibitors in the body rifabutin is recommended in patients on HAART ritonavir CYP450 inhibitor