Systemic Effects of Inflammation on Health during Chronic HIV Infection

Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are...

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Published in	Immunity (Cambridge, Mass.) Vol. 39; no. 4; pp. 633 - 645
Main Authors	Deeks, Steven G., Tracy, Russell, Douek, Daniel C.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 17.10.2013 Elsevier Limited
Subjects	Acquired immune deficiency syndrome Age Factors AIDS Anti-HIV Agents - therapeutic use Anti-Inflammatory Agents - therapeutic use Antiretroviral drugs Chronic Disease Drug therapy HIV HIV - immunology HIV Infections - complications HIV Infections - drug therapy HIV Infections - immunology HIV Infections - physiopathology Human immunodeficiency virus Humans Immunity, Innate Inflammation - etiology Inflammation - immunology Inflammation - physiopathology Intestinal Mucosa - immunology Intestinal Mucosa - physiopathology Liver - immunology Liver - physiopathology Models, Immunological Monocytes - immunology Monocytes - pathology Mortality Multiple Organ Failure - etiology Multiple Organ Failure - immunology Multiple Organ Failure - physiopathology Protein Biosynthesis - immunology Thrombophilia - drug therapy Thrombophilia - etiology Thrombophilia - immunology Thrombophilia - physiopathology
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Abstract	Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.
AbstractList	Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications, but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affect health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging. Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging. Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.
Author	Douek, Daniel C. Tracy, Russell Deeks, Steven G.
AuthorAffiliation	2 University of Vermont, Colchester, VT, USA 1 University of California, San Francisco, San Francisco, CA, USA 3 Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
AuthorAffiliation_xml	– name: 2 University of Vermont, Colchester, VT, USA – name: 1 University of California, San Francisco, San Francisco, CA, USA – name: 3 Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
Author_xml	– sequence: 1 givenname: Steven G. surname: Deeks fullname: Deeks, Steven G. email: sdeeks@php.ucsf.edu organization: University of California, San Francisco, San Francisco, CA 94114, USA – sequence: 2 givenname: Russell surname: Tracy fullname: Tracy, Russell organization: University of Vermont, Colchester, VT 05405, USA – sequence: 3 givenname: Daniel C. surname: Douek fullname: Douek, Daniel C. organization: Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24138880$$D View this record in MEDLINE/PubMed
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Snippet	Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full... Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications, but does not restore full...
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SubjectTerms	Acquired immune deficiency syndrome Age Factors AIDS Anti-HIV Agents - therapeutic use Anti-Inflammatory Agents - therapeutic use Antiretroviral drugs Chronic Disease Drug therapy HIV HIV - immunology HIV Infections - complications HIV Infections - drug therapy HIV Infections - immunology HIV Infections - physiopathology Human immunodeficiency virus Humans Immunity, Innate Inflammation - etiology Inflammation - immunology Inflammation - physiopathology Intestinal Mucosa - immunology Intestinal Mucosa - physiopathology Liver - immunology Liver - physiopathology Models, Immunological Monocytes - immunology Monocytes - pathology Mortality Multiple Organ Failure - etiology Multiple Organ Failure - immunology Multiple Organ Failure - physiopathology Protein Biosynthesis - immunology Thrombophilia - drug therapy Thrombophilia - etiology Thrombophilia - immunology Thrombophilia - physiopathology
Title	Systemic Effects of Inflammation on Health during Chronic HIV Infection
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