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
• Cardiovascular
II. Q & A

Comorbidities Associated With an
Aging 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
Eight year cross-sectional Norwegian survey subjects ≥20 yrs of age
50
GFR (mL/min/1.73 m 2 ): 30-44 <30
40
N = 65,605
30
20
10
0
20-29 30-39 40-49 50-59 60-69
Age (Years)
70-79 80-89
Adapted from Hallan SI, et al. BMJ . 2006; 333:1047-1050.
90+

Renal Disease in HIV Positive Patients
• Kidney disease is an important complication of HIV infection in the era of antiretroviral therapy 1
• 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
1 Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.
2 Gupta 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 coinfection
Wyatt, CM. AJM.
2007. 120;488-49.

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

Comorbidities Associated With an
Aging 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
Host
Age
Race
Gender
Body composition
Virus
Viral Load
Nadir CD4 levels
CDC Disease Category
Duration of HIV infection
Therapy
Duration of treatment
Certain ARVs
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 an
Aging 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 era 1
• Diabetes in HIV positive men with HAART exposure > 4X
HIV-seronegative men 2
• Risk factors for HIV positive individuals developing diabetes include 3 :
• Certain ARVs
• Older age
• Ethnic background (African American)
• Male sex
• Greater BMI
1 Florescu, D. Antiretroviral Therapy.
2007. 12:149-162.
2 Brown, TT. Arch Intern Med.
2005. 165:1179-1184.
3 DeWit, D. Diabetes Care.
2008. 31(6):1224-1229.

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 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 Webbased 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 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)
Classic
Female sex
Smoking
Decreased physical activity
Alcohol
White race
Family history
Increasing age
Amenorrhoea
/premature menopause
Decreased bone acquisition
Secondary
Chronic diseases
(e.g. hyperthyroidism, hyperparathyroidism, liver disease, rheumatological conditions, eating disorders, etc.)
Hypogonadism
Renal dysfunction
Malnutrition/low BMI
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)
• 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
Gender-adjusted rates of fracture among adults aged 25-54 years
HOPS
P value for trend = 0.01
P value for trend = 0.32
NHAMCS-
OPD
18

Comorbidities Associated With an
Aging 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.

MI Rates in HIV Positive and HIV Negative Patients
AMI rate by age group
100
80
HIV+
HIV
–
60
40
20
0
18-34 35-44 45-54 55-64 65-74
Age Group (Years)
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
Persistent
Inflammation
Endothelial
Dysfunction
Lipid Disorders
HAART
Vascular Disease in
HIV Positive Patients
ART-Associated
Lipodystrophy
= ART
= HIV Infection
= HIV Infection & ART
Viremia
Adapted from Dube M, et al. Circulation. 2008;118:e36-e40.
Oxidative Stress
Insulin
Resistance

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

Prediction of cardiovascular risk based on the
Framingham Heart Study
Risk Factor
Gender
Age
Total Cholesterol
HDL
Systolic Blood Pressure
Treatment for Hypertension (Only if SBP >120)
Current Smoker
Time Frame for Risk Estimate
Your Risk
Units male or female years mg/dL mg/dL mmHg yes or no yes or no
10 years
0,19 m
46
245
35
125 n
10
0,00 0,05 0,10 0,15 http://hin.nhlbi.nih.gov/atpiii/calculator.asp
0,20 0,25 0,30