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Comorbidities in an Aging HIV Positive Population

Comorbidities in an Aging HIV Positive Population. Brian Risley, MFA 2010 HIV Research Catalyst Forum April 21, 2010. Comorbidities Associated With an Aging HIV Positive Population. I. Comorbidities Renal Lipodystrophy Insulin Resistance / Diabetes Cancer Incidence Bone Density

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Comorbidities in an Aging HIV Positive Population

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  1. Comorbidities in an Aging HIV Positive Population Brian Risley, MFA 2010 HIV Research Catalyst Forum April 21, 2010

  2. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular II. Q & A

  3. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  4. Prevalence of Chronic Kidney Disease in the General Population Increases with Age Eight year cross-sectional Norwegian survey subjects ≥20 yrs of age GFR (mL/min/1.73 m2): 45 45-59 <30 30-44 N = 65,605 Prevalence (%) Age (Years) Adapted from Hallan SI, et al. BMJ. 2006; 333:1047-1050.

  5. Renal Disease in HIV Positive Patients • Kidney disease is an important complication of HIV infection in the era of antiretroviral therapy1 • In a retrospective study of 487 consecutive HIV positive patients with normal renal function, the initial prevalence of CKD was 2%2 • After 5 years of follow-up, 6% had progressed to CKD • Older age was a multivariate predictor of CKD for this cohort 1Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.2Gupta SK, et al. Clinical Nephrology. 2004.; 61:1-6.

  6. Kidney Disease in HIV Positive Patients • The spectrum of kidney disease in HIV includes: • HIV-associated nephropathy • Immune complex kidney disease • Medication nephrotoxicity • Kidney disease related to co-morbid conditions • Diabetes, hypertension, and hepatitis virus co-infection Wyatt, CM. AJM. 2007. 120;488-49.

  7. Risk Factors for Kidney Disease in the HIV Positive Population Ethnicity Family History Age CKD Risk Hyper- tension HIV ART Diabetes Hepatitis C = Modifiable = Nonmodifiable Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.

  8. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  9. Virus • Viral Load • Nadir CD4 levels • CDC Disease Category • Duration of HIV infection Host Age Race Gender Body composition Therapy Duration of treatment Certain ARVs Adapted from Lichtenstein KA. JAIDS. 2005;39:395–400. The Causation of Lipodystrophy Is Multi-Factorial in HIV Positive Patients

  10. Therapeutic Options for Managing Lipodystrophy • Lifestyle changes • Reduce saturated fat/ cholesterol intake • Increase physical activity • Cease smoking • Evaluate ARVs • Manage chronic co-morbid conditions • e.g. hypertension, hyperlipidemia, diabetes Falutz J., Nat Clin Pract Endocrinol Metab. 2007 Sep;3(9):651-61.

  11. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  12. Insulin Resistance and Diabetes in the HIV Positive Population • An increased prevalence of insulin resistance, glucose intolerance and diabetes has been reported in HIV infections in the HAART era1 • Diabetes in HIV positive men with HAART exposure > 4X HIV-seronegative men2 • Risk factors for HIV positive individuals developing diabetes include3: • Certain ARVs • Older age • Ethnic background (African American) • Male sex • Greater BMI 1Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.2Brown, TT. Arch Intern Med. 2005. 165:1179-1184.3DeWit, D. Diabetes Care. 2008. 31(6):1224-1229.

  13. Complications of Insulin Resistance • Insulin resistance occurs as part of a metabolic syndrome that may lead to the development of: • Type II diabetes • Atherosclerosis • Hypertension • Management: Lifestyle modification • Diabetic education • Self-monitoring of blood glucose • Aerobic and resistance training • Medication Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.

  14. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  15. Invasive cancer incidence increases by age U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2004 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2007. Available at: www.cdc.gov/uscs.

  16. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  17. Multiple risk factors for decreased BMD in the general population (HIV negative) Classic Secondary Chronic diseases (e.g. hyperthyroidism, hyperparathyroidism, liver disease, rheumatological conditions, eating disorders, etc.) Female sex Decreased physical activity Smoking Alcohol White race Hypogonadism Decreased bone acquisition Family history Renal dysfunction Increasing age Malnutrition/low BMI Amenorrhoea /premature menopause Medications (e.g. corticosteroids, anticonvulsants, anticoagulants) Bone Mineral Density Diagram adapted from Glesby MJ. Clin Infect Dis 2003; 37:S91–50

  18. Increased Fracture Rate in HIV Outpatient Study Patients (HOPS) Comparison of HOPS cohort (n=8,456) vs National Hospital Discharge Survey and National Hospital Ambulatory Medical Care Survey (NHAMCS) Adjusted for age and gender HOPS: 276 fx during median 4.8 yrs follow-up; more likely if: Age >47 Nadir CD4+ count <200 HCV co-infection Diabetes Substance use Conclusion: Fracture rates are higher in HIV+s and rate is increasing with age Gender-adjusted rates of fracture among adults aged 25-54 years HOPS P value for trend = 0.01 NHAMCS-OPD P value for trend = 0.32 Dao C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 128.

  19. Comorbidities Associated With anAging HIV Positive Population I. Comorbidities • Renal • Lipodystrophy • Insulin Resistance / Diabetes • Cancer Incidence • Bone Density • Cardiovascular

  20. Cardiovascular Disease in the HIV Positive Population • Cardiovascular (CV) disease has emerged as a health concern in the aging HIV-positive population as HAART can provide durable clinical benefit and improved survival • Contributes to more than 10% of deaths among HIV positive individuals • Factors that affect CV risk are similar for HIV positive and negative individuals • Risk may vary among ARV agents D:A:D Study Group. The Lancet. 2008. 371(9622):1417-26.

  21. 100 HIV+ 80 HIV– 60 Events per 1000 Person-Years 40 20 0 45-54 18-34 35-44 55-64 65-74 Age Group (Years) MI Rates in HIV Positive and HIV Negative Patients AMI rate by age group Cohorts (HIV+ =3851, HIV- =1,044,589) were identified in the Research Patient Data Registry. The primary outcome was AMI. Triant VA,et al. J Clin Endocrinol Metab. 2007;92:2506-2512.

  22. = ART = HIV Infection = HIV Infection & ART HIV Related Factors that May Contribute to Cardiovascular Disease Persistent Inflammation Endothelial Dysfunction Lipid Disorders HAART Vascular Disease in HIV Positive Patients ART-Associated Lipodystrophy Insulin Resistance Viremia Oxidative Stress Adapted from Dube M, et al. Circulation. 2008;118:e36-e40.

  23. Prediction of cardiovascular risk based on the Framingham Heart Study Risk Factor Units Gender male or female m Age years 46 Total Cholesterol mg/dL 245 HDL mg/dL 35 Systolic Blood Pressure mmHg 125 Treatment for Hypertension (Only if SBP >120) yes or no n n Current Smoker yes or no Time Frame for Risk Estimate 10 years 10 0,06 6% Your Risk 0,00 0,05 0,10 0,15 0,20 0,25 0,30 http://hin.nhlbi.nih.gov/atpiii/calculator.asp

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