Background:  Combined ART (cART) is associated with cardiovascular diseases. Since patients receive various drugs simultaneously, it is difficult to determine the role of each agent in the associated side effects. Clinical studies have pointed to various families as the agents responsible for these complications, the possibility that NNRTI as drugs involved in these effects remains unclear. The present study was specifically designed to analyze the acute effects of NNRTI on one of the first steps in the pathogenesis of atherosclerosis, i.e. leukocyte recruitment.

Methods: Leukocyte rolling, adhesion, and emigration were monitored in mesenteric postcapillary venules of anesthetized rats using intravital video microscopy. We analyzed the effects of the NNRTI efavirenz (EFV) and nevirapine (NVP). Drugs were administered orally 4 hours before measurements were taken and doses were chosen according to the literature in order to generate plasma levels in animals similar to those clinically present in humans:  EFV (50 mg/kg corresponding with 6 µM and 160 mg/kg corresponding with 13 µM) and NVP (50 mg/kg corresponding with 7 µM and 150 mg/kg corresponding with 17 µM). Data were compared using a 1-way analysis of variance followed by a Newman-Keuls post hoc test. Differences were considered significant when p value was <0.05. n ≥5 experiments.

Results: As shown in the table, EFV induced a significant increase on leukocyte rolling and adhesion, while it had no effect on emigration. NVP promoted significant leukocyte adhesion and emigration.

Conclusions: Acute exposure to EFV or NVP induces leukocyte recruitment, the first steps in the pathogenesis of atherosclerosis, suggesting that both drugs have the potential to generate the preliminary phases of the cardiovascular complications observed in HIV-infected patients receiving cART.