Effects of ARVs and HIV on mitochondrial function and immune activation in monocyte derived macrophages in vitro

While ART reduces HIV associated morbidity and mortality, low levels of persistent inflammation in virally suppressed individuals drive a form of accelerated aging and comorbidity. Macrophage activation drives persistent inflammation but the molecular mechanisms remain poorly understood. Uninfected and HIV-infected MDMs were treated with ARVs: TFV, 3TC, and EFV, and alterations in cell viability and mitochondrial function were characterized. Alterations were then examined for effects on inflammatory cytokine production. ARV treatment had distinct effects on mitochondrial function and metabolism. TFV increased cellular ROS, decreased cellular respiration, increased cell death, and decreased TNF-alpha. EFV decreased cellular respiration, decreased ATP production, decreased expression of complex I of the ETC, increased cell death, increased superoxide and cellular ROS, and increased TNF-alpha and IFN-beta production. In the context of HIV infection, TFV and EFV, increased cellular ROS production and TFV also decreased complex I expression of the ETC.