HIV-infected patients show functionally defective high-density lipoprotein (HDL) paralleled with changes in HDL-associated proteins

Purpose of the study: Epidemiological studies have consistently demonstrated an inverse association between plasma HDL concentrations and cardiovascular risk. Although this cardioprotective role has been mainly attributed to its role in promoting cellular cholesterol efflux, there is an emerging interest in the anti-inflammatory and antioxidant properties of HDL. The aim of the study is to investigate the anti-inflammatory properties of HDL isolated from HIV-infected patients. Methods: Cross-sectional study of 113 HIV-infected patients and 70 non-infected control subjects without evident CVD. From each subject, HDL was isolated by ultracentrifugation and its anti-inflammatory status was tested as its ability to inhibit MCP-1-induced migration of the monocytic cell line THP-1 using transwell cell culture chamber inserts with micropore filters of 5 microns pore size. HDL-associated proteins were measured by commercial ELISAs. Results: Twenty-three HIV-infected patients were ART-naive (32±15 years, 66.7% male) and ninety were currently on ART (46±11 years, 78.9 % male). Most patients on ART (91.1%) had undetectable viral load (<50 copies/mL). When compared to healthy subjects, both naive and treated HIV-infected patients had lower plasma HDL-cholesterol levels (naive: 45±12, ART: 50±10, controls: 55±10 mg/dL, p<0.05). HDL isolated from HIV naive patients showed a significantly reduced anti-inflammatory activity (THP-1 monocyte migration capacity was 203% times higher in HIV patients than in control subjects). The anti-inflammatory activity of HDL from ART-treated HIV-infected patients was significantly improved when compared to naive patients, although it remained significantly lower than controls (130% THP-1 monocyte migration vs controls). HDL from HIV-infected patients had a decreased concentration of the anti-inflammatory proteins Apo A1 (controls: 2.1±0.3, naive: 1.4±0.2, ART: 1.6±0.1 mg/ml) and LCAT (controls: 0.53±0.09, naive: 0.34±0.06, ART: 0.48±0.05 μg/ml), and increased of the pro-inflammatory protein serum amiloid (controls: 1.42±0.53, naive: 3.23±1.29, ART: 2.72±0.70 μg/ml) than healthy controls. Conclusions: Our data demonstrate HIV-infected patients, even with effective therapy, showed a marked reduction of HDL anti-inflammatory properties. This dysfunctional HDL seems to be associated with changes HDL composition and may contribute to the increased CVD risk observed in HIV infection. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Estrada V et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18271 http://www.jiasociety.org/index.php/jias/article/view/18271 | http://dx.doi.org/10.7448/IAS.15.6.18271