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Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues – gut, brain, lung – through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management.Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.