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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

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
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

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

II. Q & A

comorbidities associated with an aging hiv positive population1
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
prevalence of chronic kidney disease in the general population increases with age
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.

renal disease in hiv positive patients
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.

kidney disease in hiv positive patients
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.

risk factors for kidney disease in the hiv positive population
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.

comorbidities associated with an aging hiv positive population2
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
the causation of lipodystrophy is multi factorial in hiv positive patients
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
therapeutic options for managing lipodystrophy
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.

comorbidities associated with an aging hiv positive population3
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
insulin resistance and diabetes in the hiv positive population
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.

complications of insulin resistance
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.

comorbidities associated with an aging hiv positive population4
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
invasive cancer incidence increases by age
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.

comorbidities associated with an aging hiv positive population5
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
multiple risk factors for decreased bmd in the general population hiv negative
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

increased fracture rate in hiv outpatient study patients hops
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.

comorbidities associated with an aging hiv positive population6
Comorbidities Associated With anAging HIV Positive Population

I. Comorbidities

  • Renal
  • Lipodystrophy
  • Insulin Resistance / Diabetes
  • Cancer Incidence
  • Bone Density
  • Cardiovascular
cardiovascular disease in the hiv positive population
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.

mi rates in hiv positive and hiv negative patients
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.

hiv related factors that may contribute to cardiovascular disease
= 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.

prediction of cardiovascular risk based on the framingham heart study
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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