Effect of efavirenz on high‐density lipoprotein antioxidant properties in HIV‐infected patients

Abstract

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. AIMSA 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. METHODSThe 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. RESULTSHIV-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). CONCLUSIONSEFV-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.

HDL in Infectious Diseases and Sepsis

“…ApoL-1 traffics to the trypanosomal lysosome, where the acidic pH causes a conformational change, leading to activation of anion channel function in the apoL-1 N terminus. Lysosomal swelling kills the trypanosome (Perez-Morga et al 2005). Thus, apoL-1 confers innate immunity against this parasite (Wheeler 2010).…”

“…Also efavirenz, another NNRTI antiretroviral treatment, was 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 suggesting that ethnicity should be taken into consideration when studying drug effects on PON-1 activity (Pereira et al 2009). …”

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

“…The use of some nucleoside reverse transcriptase inhibitors (NRTI) and PIs is associated with an atherogenic lipoprotein profi le ( 35 ), but NNRTIs, such as efavirenz, promote antiatherogenic changes in HDL particles and function, including normalization of size and lipid composition, enhancement of reverse cholesterol transport, and improvement of antioxidant capacity ( 36 ). A previous study from our group showed that NNRTI treatment was associated with a relative normalization of serum apoA-I and apoA-II, as well as HDL-cholesterol concentrations, in HIV-infected patients ( 37 ), which is consistent with the reported beneficial effects of this compound on HDL composition and function.…”

Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals

“…Some studies have shown that the activity of PON1 may be affected and/or inactivated by oxidative stress, which could explain its reduced activity during HIV-1 infection [ 7 , 13 ]. In individuals infected with HIV-1 without HAART and/or with acquired immunodeficiency syndrome (AIDS), there is an increase in oxidative stress characterized by increased plasma metabolites of lipid peroxidation and/or a quantitative decrease in antioxidants compared to seronegative controls considered to be in a healthy condition [ 14 , 15 ]. Additionally, it seems that this reduction is associated with a decrease in the number of CD4+ T-cells and indicates that reduced PON1 activity is affected by the immune status of these individuals.…”