Vishrut Gulhati1, Jeremy Soo1, Doris G Ransy2, Jason Brophy3, Fatima Kakkar4, Ari Bitnun5, Lindy Samson3, Stanley Read5, Hugo Soudeyns6, Michael T Hawkes7. 1. University of Alberta, Edmonton, Alberta, Canada. 2. Unité d'immunopathologie virale, Centre de recherche du CHU Sainte-Justine, Montréal, Québec, Canada. 3. Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. 4. Faculté de médecine, Université de Montréal. 5. Department of Pediatrics, Hospital for Sick Children, University of Toronto. 6. Unité d'immunopathologie virale, Department of Microbiology, Infectiology and Immunology, Centre de recherche du CHU Sainte-Justine, Université de Montréal. 7. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Abstract
BACKGROUND: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. SETTING: Eight pediatric HIV care centers across Canada. METHODS: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. RESULTS: Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = -0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). CONCLUSIONS: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.
BACKGROUND: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. SETTING: Eight pediatric HIV care centers across Canada. METHODS: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. RESULTS:Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = -0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). CONCLUSIONS: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.
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