Changes in Plasma Levels of Oxidized Lipoproteins and Lipoprotein Subfractions with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy and Associations with Common Carotid Artery Intima-Media Thickness: ACTG 5260s

Background The role of oxidized lipoproteins (high-density [HDLox] and low-density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV-related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (?CIMT) in chronic HIV infection.Methods Prospective study of 234 HIV-infected anti-retroviral treatment-naive participants without CVD who were randomized to receive tenofovir-emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these bio-markers with dCIMT were analysed with mixed effects linear regression.Results HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between ?CIMT and oxidized lipoproteins at all time points were not apparent (P=0.10). There was some evidence of slower ?CIMT for higher HDLp number (P=0.06) and for lower LDLp number (P=0.08) measured at baseline.Conclusions Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with ?CIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study.