Effect of Efavirenz on High-Density Lipoprotein Antioxidant Properties in HIV-Infected Patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients. * Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events. * Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function. WHAT THIS STUDY ADDS: * In the present work, we studied the effect of EFV on the activity of PON-1 and showed, for the first time, that EFV-based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON-1 activity. AIMS: A long-term and concentration-dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high-density lipoprotein (HDL-c) in human immunodeficiency virus (HIV)-infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL-c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON-1 in HIV-infected patients. METHODS: The patients included were adults with a documented HIV-1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL-c and CD4 cell count on PON-1 activity was analysed. RESULTS: HIV-infected White patients treated with EFV had higher PON-1 activity [77.35 U l(-1) (65.66, 89.04)] (P < 0.05) and higher PON-1 activity : HDL-c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON-1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml(-1) (P= 0.0120). CONCLUSIONS: EFV-based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON-1 activity. The PON-1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON-1 activity.

The Proarrhythmic Effect of Cardiac Resynchronization Therapy: an Issue that Should Be Borne in Mind

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system.