Comorbidities in an Aging HIV Positive Population

Brian Risley, MFA

2010 HIV Research Catalyst Forum

April 21, 2010

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 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

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+

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

• 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.

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.

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

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.

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 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

• 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)

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 anAging HIV Positive Population

I. Comorbidities

• Renal

• Lipodystrophy

• Insulin Resistance / Diabetes

• Cancer Incidence

• Bone Density

• Cardiovascular

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 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)

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

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.

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 (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.

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

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

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

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