Efavirenz treatment causes arterial stiffening in apolipoprotein E-null mice

The development of highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a terminal diagnosis to a chronic, yet manageable disease. However, people living with HIV-1 exhibit a host of non-AIDS-related co-morbidities including cardiovascular disease (CVD). Several HAART drugs have been implicated in the development of CVD; however, the role of efavirenz (EFV), a highly prescribed HAART drug, in early-onset CVD is poorly understood. We treated apolipoprotein E-null (ApoE(-/-)) mice with EFV (75 mg/kg/day) or vehicle, via oral gavage, for 35 days and quantified commonly measured preclinical markers of CVD (intima-media thickening, arterial stiffening) and plaque area. Suprarenal abdominal aortas were subjected to cylindrical biaxial biomechanical testing and standard histology. Aortas from EFV-treated mice demonstrated decreased compliance (i.e., increased arterial stiffness) and decreased axial force and a trend toward decreased in vivo axial stretch, but EFV treatment had no effect on intima-media thickness of the aortic wall or plaque coverage in thoracic aortas and aortic arches. Taken together, these data suggest that EFV leads to arterial stiffening but, for the dose and duration tested, did not lead to elevated plaque progression in ApoE(-/-) mice.