HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque.

BACKGROUND: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk.

METHODS: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL.

RESULTS: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ±0.01 versus 1.3 ±0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects (P=0.03).

CONCLUSIONS: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to non-calcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk.

CLINICAL TRIAL REGISTRATION NUMBER: NCT 00455793.