Comorbidities in an Aging HIV Positive Population

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
45
lt30
GFR (mL/min/1.73 m2)
45-59
30-44
N 65,605
Prevalence ()
Age (Years)
Adapted from Hallan SI, et al. BMJ. 2006
3331047-1050.
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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 22
• 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 401559-1585.2Gupta SK, et al. Clinical
Nephrology. 2004. 611-6.
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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. 120488-49.
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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 401559-1585.
8
Comorbidities Associated With anAging HIV
Positive Population

• I. Comorbidities
• Renal
• Lipodystrophy
• Insulin Resistance / Diabetes
• Cancer Incidence
• Bone Density
• Cardiovascular

9
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
Sep3(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
  gt 4X HIV-seronegative men2
• Risk factors for HIV positive individuals
  developing diabetes include3

• Male sex
• Greater BMI

• Certain ARVs
• Older age
• Ethnic background (African American)

1Florescu, D. Antiretroviral Therapy. 2007.
12149-162.2Brown, TT. Arch Intern Med. 2005.
1651179-1184.3DeWit, D. Diabetes Care. 2008.
31(6)1224-1229.
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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.
12149-162.
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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 19992004 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 37S9150
18
Increased Fracture Rate in HIV Outpatient Study
Patients (HOPS)

• Comparison of HOPS cohort (n8,456) 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 gt47
• Nadir CD4 count lt200
• HCV co-infection
• Diabetes
• Substance use
• Conclusion Fracture rates are higher in HIVs
  and rate is increasing with age

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

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

DAD Study Group. The Lancet. 2008.
371(9622)1417-26.
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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.
2007922506-2512.
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HIV Related Factors that May Contribute to
Cardiovascular Disease
Endothelial Dysfunction
Persistent Inflammation
Lipid Disorders
HAART

Vascular Disease in HIV Positive Patients
ART-Associated Lipodystrophy
Insulin Resistance
Oxidative Stress
Viremia
Adapted from Dube M, et al. Circulation.
2008118e36-e40.
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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 gt120)
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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