Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

Figure 1 The human immunodeficiency virus type 1, upon entering peripheral circulation, will infect lymphocytes and macrophages. The viral proteins gp120 and gp41 of HIV-1 bind to the CD4+ receptor and coreceptors, C-C chemokine receptor type 5 and C-X-C chemokine receptor type 4, on the surface of these cells. The lymphocytes T-CD4 that are infected with HIV-1 produce viral particles and may remain in a latent form within circulation. Infected monocytes can directly present antigen to lymphocytes T-CD4, or transform into tissue macrophages. This process stimulates the host inflammatory response and amplifies the production of proinflammatory cytokines and promotes increased cellular oxidative stress. The production of proinflammatory cytokines by macrophages and lymphocytes promotes a decrease in plasma high-density lipoprotein cholesterol by impairing the cholesterol dependent efflux transporter ATP-binding cassette protein A1 in human macrophages. Additionally, viral proteins and proinflammatory cytokines including interleukin-1, interleukin-6, tumor necrosis factor α and interferon gamma stimulate endothelial lipase enzyme and different acute phase proteins, such as serum amyloid A. Viral proteins also exert effects on adipocytes resulting in mitochondrial dysfunction, production of reactive oxygen species, increased insulin resistance, decreased adiponectin, and change the clearance of triglyceride-rich lipoproteins and insulin resistance. Finally, all of the different cellular mechanisms involved and affected by HIV-1 infection promote an increased risk of cardiovascular disease. Source: de Almeida et al[211]. Gp120: Glycoprotein 120; gp41: Glycoprotein 41; CCR5: C-C chemokine receptor type 5; CXCR4: C-X-C chemokine receptor type 4; LT-CD4: Lymphocytes T-CD4; HDL: High-density lipoprotein; ABCA1: ATP-binding cassette protein A1; IL-1: Interleukin-1; IL-6: Interleukin-6; TNFα: Tumor necrosis factor α; IFN-γ: Interferon gamma; TG-RLP: Triglyceride-rich lipoproteins; ROS: Reactive oxygen species; HIV-1: Human immunodeficiency virus type 1.