Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus: ACTG NWCS332

The role of high-density lipoprotein (HDL) function and advanced glycation end products (AGEs) in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. Both glycation and oxidation (HDL(ox)) are major modifications of HDL that can alter its composition and function. Therefore, we explored the longitudinal association of HDL(ox) with progression of glycation, as evaluated by measurement of circulating forms of receptor for AGE that predict morbidity (soluble Receptors for Advanced Glycation Endproducts [sRAGE], endogenous secretory Receptors for Advanced Glycation Endproducts [esRAGE]), in people with HIV-1 (PWH; HIV-1(+)) and uninfected (HIV-1(−)) individuals. We retrospectively assessed if levels of plasma sRAGE and esRAGE and HDL function (reduced antioxidant function is associated with increased HDL lipid hydroperoxide content; HDL(ox)) in a subset of participants (n = 80) from a prospective 3-year study (AIDS Clinical Trials Group A5078). Primary outcomes were baseline and yearly rates of change over 96 of 144 weeks (Δ) in HDL(ox) in HIV-1(+) versus uninfected HIV-1 controls (noted as HIV-1(−)). Higher baseline levels of sRAGE in PWH on effective anti-retroviral therapy and with low CVD risk, but not in HIV-1(−) persons, were independently associated with higher HDL(ox). EsRAGE, but not sRAGE, had consistent inverse relationships with ΔHDL(ox) in both HIV-1(+) and HIV-1(−) persons at baseline. In HIV-1(−) but not in HIV-1(+) persons, ΔHDL(ox) had positive and inverse relationships with ΔRAGE and ΔesRAGE, respectively. Glycation and oxidation of HDL may contribute to impaired HDL function present in PWH.