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The role of treatment versus disease in causing premature non-AIDS morbidity

The role of treatment versus disease in causing premature non-AIDS morbidity . Judith S. Currier, MD University of California, Los Angeles. Serious Non AIDS Events. Growing cause of morbidity and mortality but still relatively rare

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The role of treatment versus disease in causing premature non-AIDS morbidity

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  1. The role of treatment versus disease in causing premature non-AIDS morbidity Judith S. Currier, MD University of California, Los Angeles

  2. Serious Non AIDS Events • Growing cause of morbidity and mortality but still relatively rare • More common than AIDS events among treated cohorts J Neuhaus et al AIDS 2010 • Related to immunodeficiency • Heterogeneous group of diseases, some common etiologies

  3. Factors Associated with NCD in HIV HOST/ LIFESTYLE VIRUS/IMMUNE SYSTEM ART Understanding the relative contributions of each of these factors to the pathogenesis of complications in HIV will help to inform the development of strategies for prevention and treatment

  4. Serious Non-AIDS Events • Cardiovascular Disease • Renal Disease • Hepatic Disease • Malignancy

  5. Serious Non-AIDS Events • Cardiovascular Disease • Renal Disease • Hepatic Disease • Malignancy

  6. Summary of HIV, Host and ART Effects HIV Replication ART Effects Microbial translocation Immune Activation Inflammation Altered Lipids Endothelial Function Macrophage recruitment Insulin Resistance HIV (nef) Atherosclerosis Smoking Hypertension Genetics

  7. Cardiovascular Disease IMMUNE SYSTEM HOST/ LIFESTYLE ART Age, Genetics, lifestyle, environment may overshadow contributions of ART and immune activation/inflammation In high risk- predisposed individual- contributions of ART may be Magnified

  8. Risk Factors for MI in D:A:D DAD Study Group. N Engl J Med 2007; 356:1723.

  9. HIV and CRP both predict MI risk Triant et al, J Acquir Immune Defiic Syndr, 2009 (adapted)

  10. Low HDL contributes to CVD Risk Estimates in HIV Cotter AG et al AIDS 2011 Mar 27;25(6):867-9

  11. Way Forward • Role of ART • Does treatment at higher CD4 prevent non-AIDS events? • Ongoing RCTs of treatment at CD4 > 500 • RCTs can also compare contribution of different ART regimens • Role of immune activation/inflammation • Studies to dampen immune activation and inflammation can probe whether surrogates of non-AIDS events are improved, ultimately will need clinical endpoint studies

  12. Current Approach • Manage known traditional risk factors for serious non-AIDS events • Smoking • Hypertension • Obesity, excess visceral fat • Diabetes

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