Comorbidities in an Aging HIV Positive Population
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Comorbidities in an Aging HIV Positive Population
Brian Risley, MFA
2010 HIV Research Catalyst Forum
April 21, 2010
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
II. Q & A
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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Prevalence of Chronic Kidney Disease in the General Population Increases with Age
Adapted from Hallan SI, et al. BMJ. 2006; 333:1047-1050.
Age (Years)
45 <30
Pre
vale
nce
(%
)
GFR (mL/min/1.73 m2): 45-59 30-44
Eight year cross-sectional Norwegian survey subjects ≥20 yrs of age
N = 65,605
0
10
20
30
40
50
20-29 30-39 40-49 50-59 60-69 70-79 80-89 90+
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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.
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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.
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AgeFamily History
ART Diabetes
HIV Hyper- tension
Hepatitis C
Ethnicity
CKD Risk
= Modifiable= Nonmodifiable
Risk Factors for Kidney Disease in the HIV Positive Population
Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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The Causation of Lipodystrophy Is Multi-Factorial in HIV Positive Patients
TherapyDuration of treatment
Certain ARVs
HostAgeRace
GenderBody composition
VirusViral Load
Nadir CD4 levelsCDC Disease Category
Duration of HIV infection
Adapted from Lichtenstein KA. JAIDS. 2005;39:395–400.
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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.
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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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:
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.
• Male sex• Greater BMI
• Certain ARVs• Older age• Ethnic background (African American)
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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.
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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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.
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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Multiple risk factors for decreased BMD in the general population (HIV negative)
Female sex Decreased physical activity
Decreased bone acquisition
Smoking
White race
Family history
Alcohol
Increasing age
Amenorrhoea /premature menopause
Classic
Hypogonadism
Malnutrition/low BMI
Renal dysfunction
Secondary
Medications (e.g. corticosteroids, anticonvulsants, anticoagulants)
Chronic diseases (e.g. hyperthyroidism, hyperparathyroidism, liver disease, rheumatological conditions, eating disorders, etc.)
Bone Mineral Density
Diagram adapted from Glesby MJ. Clin Infect Dis 2003; 37:S91–50
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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
NHAMCS-OPD
P value for trend = 0.01
P value for trend = 0.32
Dao C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 128.
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Comorbidities Associated With anAging HIV Positive Population
I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular
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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.
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Triant VA,et al. J Clin Endocrinol Metab. 2007;92:2506-2512.
MI Rates in HIV Positive and HIV Negative Patients
Age Group (Years)
Eve
nts
per
10
00 P
erso
n-Y
ears
20
40
60
80
100
0
18-34 35-44 45-54 55-64 65-74
HIV+
HIV–
Cohorts (HIV+ =3851, HIV- =1,044,589) were identified in the Research Patient Data Registry.
The primary outcome was AMI.
AMI rate by age group
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HIV Related Factors that May Contribute to Cardiovascular Disease
Adapted from Dube M, et al. Circulation. 2008;118:e36-e40.
= HIV Infection
= ART
= HIV Infection & ART
Endothelial Dysfunction
HAART
Persistent Inflammation
Oxidative Stress
Vascular Disease in HIV Positive Patients
Lipid Disorders
ART-Associated Lipodystrophy
Insulin Resistance
Viremia
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Risk Factor Units
Gender male or female mAge years 46Total Cholesterol mg/dL 245HDL mg/dL 35Systolic Blood Pressure mmHg 125Treatment for Hypertension (Only if SBP >120) yes or no nCurrent Smoker yes or no nn
Time Frame for Risk Estimate 10 years 10
Your Risk 0,06 6%6%
0,00 0,05 0,10 0,15 0,20 0,25 0,30
http://hin.nhlbi.nih.gov/atpiii/calculator.asp
Prediction of cardiovascular risk based on the Framingham Heart Study
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Prediction of cardiovascular risk based on theFramingham Heart Study
Risk Factor Units
Gender male or female mAge years 46Total Cholesterol mg/dL 245HDL mg/dL 35Systolic Blood Pressure mmHg 125Treatment for Hypertension (Only if SBP >120) yes or no nCurrent Smoker yes or no yy
Time Frame for Risk Estimate 10 years 10
Your Risk 0,19 19%19%
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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