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

Abstract

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

Fig. 1.

(A) Serum PON3 concentrations in control subjects and HIV-infected patients. (B) ROC plot for serum PON3 concentration measurement in HIV-infected and noninfected subjects. AUC, Area-under-the curve; CI, Confidence interval. (C) Relationship between serum PON3 concentrations and oxidized LDL levels (ox-LDL) in HIV-infected patients.

Fig. 2.

FPLC lipoprotein fractionation and PON3 lipoprotein distribution in the control and the HIV-infected pools.

Fig. 3.

Relationships among serum PON3 concentrations, β-2-microglobulin concentrations, and the duration of nonnucleoside reverse transcriptase inhibitors (NNRTI) in HIV-infected patients.