Differential Effects of Tenofovir/Emtricitabine and Abacavir/Lamivudine on Human Leukocyte Recruitment

Abstract

The association of abacavir (ABC) with cardiovascular disease has led to HIV treatment guidelines favouring the combination of tenofovir/emtricitabine (TDF/FTC) over that of ABC/lamivudine (ABC/3TC). We have analysed the effects of plasma-relevant concentrations of TDF, FTC, ABC and 3TC, individually and in clinically employed combinations, on human leukocyte accumulation. The effects of ABC, 3TC, TDF and FTC on the expression of adhesion molecules were also evaluated. Interactions between human leukocytes - specifically peripheral blood polymorphonuclear or mononuclear cells - and human umbilical vein endothelial cells were evaluated in a flow chamber reproducing in vivo conditions. The expression of adhesion molecules was analysed by flow cytometry. Concentrations of TDF, FTC or 3TC mimicking those in the plasma of patients did not have any effect on human leukocyte-endothelial cell interactions, while contrasting results were obtained with ABC. This distinct pattern was reproduced when the drugs were administered in combination; namely, ABC/3TC had a significant influence on rolling and adhesion while TDF/FTC did not. However, the effects produced by ABC alone did not differ when it was combined with 3TC, which suggests the former drug was responsible for the effects observed. ABC, 3TC, TDF and FTC did not modify the expression of endothelial adhesion molecules. Conversely, only ABC enhanced the expression of leukocyte CD11b/CD18 in neutrophils and monocytes. Our results provide evidence that the combination TDF/FTC has a better vascular profile than ABC/3TC.