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

Abstract

Background. Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV; n = 195) or nevirapine (NVP; n = 95) or lopinavir/ritonavir (LOP/r; n = 219). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. Results. PON1 activity (U/L) was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r = 0,121; P = 0,014). The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio) in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

The Effects of Treatment on Serum Hepcidin and Iron Homeostasis in HIV-1-Infected In-dividuals

“…HIV-1 RNA levels and CD4 + T-cell numbers are indicators of the clinical stage of infection and are considered prognostic factors for the evaluation of the course of HIV-1 infection [16] [17]. The maintenance of CD4 + T-cell and CD8 + T-cell numbers characterizes the efficacy of HAART, which inhibits viral replication, slows the progression of immunodeficiency, and therefore restores immunity and increases the quality of life for HIV-1-infected individuals [18] [19]. Therefore, it is possible to infer a relationship between the number of CD4 + T-cells and serum hepcidin levels, which would be directly related to the best course of HIV-1 infection.…”

“…However, this hypothesis does not take into account the reduced levels of hepcidin, iron and ferritin observed in our ART-naïve group because those groups with different HAART regimens containing AZT did not display changes in the levels of these parameters, nor did these groups have any type of anemia or changes in iron metabolism. We can with some degree of certainty consider that modern HAART treatment can considerably overcome many of these effects [17] [19] [32].…”

The Impact of Modern Antiretroviral Therapy on Lipid Metabolism of HIV-1 Infected Patients

“…The hypothesis that the PIs can promote reductions in the activity of PONs and an increased risk for atherosclerotic disease in HIV-1 patients has been shown through previous evidence. PON1 is an antioxidant enzyme present in serum is strongly associated with apolipoprotein-A1 (apoAl) from HDL and protects LDL against oxidative modifications [69,70]. The action of serum PON1 most likely occurs through the involvement of the enzyme in reverse cholesterol transport, a well-established anti-atherogenic propriety of HDL [71].…”

“…The inhibition of oxLDL by HDL is attributed to the high antioxidant content of the lipoprotein possibly due to the antioxidant properties of apoA1 and by the presence of other different antioxidant enzymes, such as glutathione peroxidase and PON, which prevent the formation of or degrade bioactive products of oxLDL [68]. 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 [69][70][71]. In HIV-1 patients and those who undergo HAART, there is a significant increase in oxidative stress.…”

“…In asymptomatic HIV-1 patients, there is an increased oxidative stress characterized by elevated lipid peroxidation products and/or a quantitative decrease in antioxidants compared to seronegative controls that are considered to be in a healthy condition. Therefore, possible reductions in the activity of PON1 and HDL concentrations may characterize an increased cardiovascular risk in individuals infected with HIV-1 [70,71,75]. The PON1 activity that was reduced in ART-naïve patients, and restored in patients treated with HAART suggested that the activity of PON1 is associated with the immune status in HIV-1 patients.…”