P5343The presence of anti-apolipoprotein A1 autoantibodies is associated with a pro-atherogenic profile in HIV-infected patients

Abstract

Abstract Background With the access to antiretroviral therapy (ART), the mortality related to the human immunodeficiency virus (HIV) has dropped, shifting the clinical challenges towards chronic disease management, including cardiovascular disease (CVD) risk assessment. Factors that potentially contribute to the physiopathology of HIV-related CVD include the HI-virus itself, adverse effects of ART, and processes such as dyslipidemia, inflammation, immune/autoimmune activation and endothelial injury. Among autoantibodies of possible cardiovascular relevance, those directed against apolipoprotein A-1 (anti-apoA-1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis. Purpose The aim of the study was to evaluate the prevalence of anti-apoA1 IgG in HIV-free and ART experienced and naïve HIV-infected patients as well as the association between anti-apoA1 IgG levels and, indices of viral suppression, clinical parameters (10 year Framingham Risk Score (FRS)) and inflammatory biomarkers, known to underlie atherosclerosis burden in these patients. Methods Anti-apoA1 IgG serum levels were assessed by a homemade ELISA assay in 144 participants from a South African cohort divided in three groups: HIV-free (n=50), HIV-infected/ART experienced (n=50) and HIV-infected/ART naïve (n=44). Inflammatory biomarkers were measured. Results HIV-infected patients displayed an increased pro-atherogenic biomarker profile compared to HIV-free subjects, but not difference in the FRS was observed between these two groups. Regarding anti-apoA1 IgG, 24% of HIV-free patients tested positive compared to 40% and 70% in HIV-infected/ART experienced and naïve groups, respectively. HIV-infected, anti-apoA1 IgG positive patients showed a significant decrease in CD4+ counts (p=0.003) and a significant increase in viremia (p=0.0130), mean heart rate (p=0.0243), albuminuria (p=0.0155), pro-inflammatory biomarkers (IFNγ, IL-10, TNFα, MIPα; all p<0.05), circulating levels of intercellular adhesion molecule (ICAM-1) (p=0.0217) and vascular cell adhesion molecule (VCAM-1) (p=0.003) compared to anti-apoA1 IgG negative ones. Of note, while this profile was maintained in HIV-infected/ART experienced, these significant differences were lost in HIV-infected/ART naïve patients. No significant difference in FRS was observed between anti-apoA1 IgG positive vs negative individuals in all groups. Conclusions HIV-infected patients presented with an increased prevalence of anti-apoA1 IgG compared to HIV-free subjects. In HIV-infected/ART experienced patients, anti-apoA1 IgG levels were associated with low CD4+ counts, levels of adhesion molecules and pro-inflammatory responses, features associated with increased cardiovascular events. ART highlighted pro-atherogenic differences between HIV-infected anti-apoA1 IgG negative and positive patients.