13 Another example of the same accelerated aging process is the telomere length of CD4+ and CD8+ T cells in HIV carriers, which resembles the telomere length of HIV-negative patients 38 years older.14 Chronic activation of the immune system probably contributes to the accelerated aging in HIV-infected patients.15 The chronic inflammatory process caused by the

persistent immune activation is associated with the increased release Inhibitors,research,lifescience,medical of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α as well as pro-coagulants such as cystatin-C and D-dimer.16 These plasma biomarkers of inflammation decline dramatically with combination antiretroviral therapy (cART) administration, but do not normalize entirely.17 Chronic inflammatory manifestations are also seen in physiological aging and have been implicated in the development of cardiovascular disease in aged people. Chronic inflammation may also serve as a proximate mediator to functional decline,18 and to frailty development in aging.19 Inhibitors,research,lifescience,medical NON-AIDS COMPLICATIONS IN AGING HIV-INFECTED PATIENTS One of the important studies of the

ART era was the Strategies for Management of Antiretroviral Therapy (SMART).20 It was designed to compare two treatment strategies: one which was viral suppressive and continuous Inhibitors,research,lifescience,medical regardless of CD4 count; the other with treatment interruptions according to CD4 levels. After a mean follow-up period of 16 months, the study review board recommended to stop enrollment to the trial because of a safety risk in the treatment Inhibitors,research,lifescience,medical interruption group. The statistical analysis showed that patients in the interruption group had an increased risk of mortality, both from click here opportunistic infections and from cardiovascular, renal, or hepatic disease. This study demonstrated the health effects of HIV beyond AIDS-defining illnesses. METABOLIC CHANGES AND CARDIOVASCULAR DISEASE The HIV-positive population experiences both external and internal metabolic changes. Abnormal fat distribution, also known Inhibitors,research,lifescience,medical as lipodystrophy, occurs in both treated21 and untreated22 HIV-positive patients. It includes two

different syndromes: lipoatrophy, or subcutaneous almost fat loss of face, extremities, and buttocks; and lipohypertrophy, or central fat deposition, manifested as intra-abdominal (visceral) fat, buffalo hump, or breast enlargement. The risk factors for the two abnormal fat distribution syndromes are different. According to the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, lipoatrophy can be found in almost 40% of HIV-positive men23 and 30% of HIV-positive women.24 Patients at higher risk to develop lipoatrophy are the ones with lower BMI (body mass index), higher nadir HIV load, and use of ART, especially stavudine, zidovudine, and earlier protease inhibitors (PIs).25 Lipohypertrophy is more common in HIV-positive women than HIV-positive men and in individuals with greater body fat levels to begin with.