HIV patients on effective antiretroviral therapy are often at an increased risk of cardiovascular complications, possibly attributed to off-target drug effects. Previous studies have associated antiretroviral treatment with increased risk of endothelial dysfunction and myocardial infarction, but a link between antiretrovirals and endothelial function has not been established yet. The aim of this study was to determine the effects of antiretrovirals in everyday clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV.
Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulfate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. TF and ectonucleotidase activities were measured using colorimetric plate-based assays. ABC-treated cells and EMP had more significant TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. The collective data establishes a pharmacological link between ABC and increased endothelial activation following inflammatory stimulation.
These observations, along with earlier studies demonstrating ABC’s effect upon platelet activation, suggest specific antiretroviral-associated functional mechanisms that underpin the ABC-associated CVD risk reported within the literature. In contrast to TAF, TDF, and ABC and do not affect endothelial cells or increase cardiovascular risk. However, their effects on ectonucleotidases do suggest potentially cardioprotective effects.