1. People living with HIV have immune activation that contributes to the pathogenesis of cardiovascular disease.
Work completed by HMRG has shown that people with HIV have an activated immune system that is not corrected with antiretroviral therapy and that this immune activation is characterised by abnormalities linked to increased risk of cardiovascular disease.
O'Halloran JA, Dunne E, Gurwith M, Lambert JS, Sheehan GJ, Feeney ER, et al. The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection. HIV Med 2015,16:608-619.
2. Cells of people living with HIV have signals which suggest abnormal cholesterol metabolism.
Cells called monocyte / macrophages, important in the pathogenesis of cardiovascular disease, contribute to atherosclerosis by retaining cholesterol which then becomes embedded in the walls of blood vessels. Work led by HMRG involving research sites in Dublin, London and Amsterdam has shown that in people with HIV, monocytes have an abnormal gene signature that suggests their cells have too much cholesterol and these abnormalities are not corrected with antiretroviral treatment. These findings have identified specific targets that may be used in the treatment of these abnormalities in people with HIV.
O'Halloran JA, Maughan RT, Feeney ER, Lambert J, Sheehan G, Moyle G, et al. Dysregulated Monocyte Cholesterol Metabolism Gene Expression With ART Initiation. CROI 2016, Boston, MA 2016,Abstract 665.
Feeney ER, McAuley N, O'Halloran JA, Rock C, Low J, Satchell CS, et al. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation. J Infect Dis2013,207:628-637
3. Some antiretroviral treatments may also alter the risk of cardiovascular disease.
Groundbreaking research conducted by HMRG scientists in collaboration with scientists from the Royal College of Surgeons in Ireland have identified an association between a commonly used antiretroviral drug and activity of platelets, which are important in how the blood clots. Abnormalities in platelet function may increase an individual's risk of heart disease and these findings may explain observations from large international studies linking use of this drug with increased cardiovascular disease.
Satchell CS, O'Halloran JA, Cotter AG, Peace AJ, O'Connor EF, Tedesco AF, et al. Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy. J Infect Dis 2011,204:1202-1210.
O’Halloran JA, Dunne E, Tinago W, Denieffe S, Kenny D, Mallon PWG. Effect of Switch from Abacavir to Tenofovir DF on Platelet Function Markers: a SWIFT Trial Sub-study. CROI, Boston, MA 2014:Abstract 749LB.