Which class of HIV medications is commonly associated with lipodystrophy and metabolic side effects?

• A. NRTIs
• B. INSTIs
• C. Protease inhibitors
• D. NNRTIs

Answer: (C)

Protease inhibitors are the class most commonly linked to HIV lipodystrophy and metabolic disturbances. Patients on older PI regimens often develop a syndrome of fat redistribution—loss of subcutaneous fat in the face, arms, and legs with concurrent central fat buildup in the trunk and dorsocervical region (the buffalo hump). This body fat change goes hand in hand with metabolic issues like high triglycerides, elevated cholesterol, and insulin resistance that can lead to type 2 diabetes. The mechanism is multifactorial, involving effects on adipocyte differentiation and lipid metabolism, and can include insulin signaling disruption. While other antiretroviral classes can cause lipid changes, the combination of fat redistribution and dyslipidemia is most characteristic of protease inhibitors. Newer regimens have improved metabolic profiles but the association with lipodystrophy remains the classic link.