Modern antiretroviral treatment belongs to the greatest success of current medicine. HIV infection has gone from a death sentence to a manageable chronic disease which develops several decades. Thanks to treatment advances, people with HIV can and do live long and full lives. In the last two decades, the incidence AIDS defining illnesses have been dramatically reduced especially opportunistic infections and malignancies, whereas the role of non-infection comorbidities has risen than age-matched HIV uninfected adults. These comorbidities include cardiovascular diseases, venous and arterial thrombosis, metabolic disorders, chronic liver and renal diseases, nervous system disorders, osteoporosis and some cancers. This relatively large group of diseases is known as non-AIDS defining or indicating diseases and these diseases are associated in HIV uninfected general population with older age and ageing Most HIV positive individuals on antiretrovirals present an abnormal level of immune activation, inflammation and hypercoagulable condition. These hallmarks are typically seen in older HIV uninfected general population and are associated with aging and the immunosenescent phenotype. The explanation for this phenomenon is unclear. There are multiple factors, which may apply pathophysiologically, including the residual immune dysregulation syndrome and antiretrovirals alone. It is clear that changes in the nature of chronic HIV infection put it in internal medicine. Cardiology, internal medicine, geriatric and oncology syndromes are dominating manifestations in HIV positive patients on antiretrovirals. Care management for HIV infected individuals will need to draw on a wide range of medical disciplines in diagnosis and treatment. Clarification of these phenomena would be beneficial for the treatment of these non-infectious diseases in HIV positive and as well in HIV negative general population.Key words: antiretroviral therapy - HIV infection - immune dysregulation - immunosenescence - non-AIDS disease.

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