1. Comorbidities in an Aging HIV Positive Population
Fernando Garcia, MD
Valley AIDS Council
HalingenTExas

2. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 2

3. HAART & An Aging HIV Positive Population
The success of HAART has dramatically enhanced life expectancy among HIV positive individuals1
By 2015, it is estimated that more than one-half of all HIV positive individuals in the US will be aged >50 years2
Objective: To establish that HAART has increased the life expectancy of HIV positive individuals, and the percentage of these patients >50 years of age is increasing.
Transition: Show the data demonstrating the increase in average age in the HIV positive population over time.
1Munoz A, et al. AIDS. 1997;11:S69-76.
2Statement from Senator Gordon H. Smith. Aging hearing: HIV over fifty, exploring the new threat. Available at: Accessed September 25, 2008.

4. Age Distribution (in years) of HIV Positive Individuals Living in the United States
Objective: Graphically depict the aging of the HIV positive population.
Transition: Not only are people living longer, but fewer people are dying from AIDS-related conditions
Adapted from CDC Surveillance Report 2006

5. Rate of HIV Related Deaths Have Declined Since 1999
Overall deaths
HIV-related deaths
Non-HIV-related deaths
900
800
700
600
500
400
300
200
100
1999
2000
2001
2002
2003
2004
Years
Rate per 10,000 persons with AIDS
Age-adjusted AIDS mortality rate by underlying cause of death
Objective: Illustrate that the percentage of overall deaths for non-AIDS defining illnesses in HIV positive patients is increasing over time.
Background
A population-based analysis was conducted from 1999 through 2004 utilizing the New York City HIV/AIDS Reporting System and Vital Statistics Registry (N=68,669). The population included patients ≥13 years of age who received a diagnosis of AIDS; were alive at any time between 1999 and 2004; and, among those who died, had a known underlying cause of death (98.2%).
Transition: Setting up why certain co-morbidities are important to factor into to treating HIV infected patients.
1 out of 4 deaths of patients with AIDS was non-HIV related
The proportion of deaths due to non-HIV related causes increased over this time period
Sackoff JE, et al. Ann Interm Med. 2006;145: 5

6. Comorbidities Associated with an Aging HIV Positive Population
Age related comorbidities are important in HIV positive individuals:
Renal1
Lipodystrophy2
Insulin Resistance / Diabetes3
Cardiovascular4
These comorbidities in HIV positive patients may be increasingly important in determining the course of therapy in an aging patient population
Objective: Summary slide, creating a call to action for considering common age related comorbidities when treating HIV positive patients.
Transition: Introduce case study
1Gupta SK, et al. Clinical Infectious Disease ; 40: ,
2Falutz J., Nat Clin Pract Endocrinol Metab Sep;3(9):
3Florescu, D. Antiretroviral Therapy :
4Schambelan M et al. Circulation. 2008;118:e48-e53.

7. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 7

8. Case Study: Treatment-Experienced Patient
Patient is a 63-year-old African American man who presents to the office for routine follow-up
HIV positive for 6 years and has been on a BID boosted PI-based antiretroviral regimen since diagnosis
No history of prior treatment intolerance or virologic failures
He describes mild long-standing fatigue and infrequent episodes of diarrhea
Current labs:
CD4+ = 436 cells/mm3, VL <50 copies/mL,
WBC = 5.2 cells/μL, Hgb = 14.1g/dL, Platelet count = 236,000
TC = 212 mg/dL, TG = 190 mg/dL, LDL = 123 mg/dL, HDL = 41 mg/dL
FBG = 120mg/dl, Creatinine = 1.2 mg/dL, BUN = 6 mg/dL, Normal LFTs
eGFR (C-G method) = 78.8 mL/min/1.73 m2
Objective: Introduce a 63 y/o HIV patient who has slightly elevated risk for both cardiovascular disease and renal disease.
Transition to physical exam and reason for patient visit.

9. Case Study: Treatment-Experienced Patient
Current meds: ARV regimen, statin, PRN antidiarrheal
No history of diabetes, HTN, tobacco use, or family history of CAD
Physical exam: lipoatrophy of face, arms, and legs; Waist circumference = 39”
Patient is starting a new job and has concerns about his current ARV regimen
Objective: Complete medical history and describe patient visit to provider
Transition: Questions to consider for this patient.

10. Case Study: Treatment-Experienced Patient
How does this patient’s age affect your initial evaluation?
How do his physical exam and lab values factor into treatment decisions?
What are the similarities and differences in how you would manage this patient compared to a younger patient?

11. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 11

12. 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):
45-59 45
30-44
<30
N = 65,605
Prevalence (%)
Objective:
The proportion of the general population with chronic kidney disease increases dramatically with age.
Transition:
Describe how CKD manifests in HIV positive patients
Age (Years)
Adapted from Hallan SI, et al. BMJ. 2006; 333:

13. 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
Objective: Highlight the fact that kidney disease is prevalent in the aging HIV positive population.
Transition: How does this compare to the general (non-HIV positive) population?
1Gupta SK, et al. Clinical Infectious Disease ; 40: Gupta SK, et al. Clinical Nephrology ; 61:1-6.

14. 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
Objective: Causation of kidney disease in HIV positive patients is multi-factorial
Transition: There are many risk factors associated with CKD
Wyatt, CM. AJM ;

15. Risk Factors for Kidney Disease in the HIV Positive Population
Ethnicity
Family History
Age
CKD Risk
HIV
Hyper- tension
Diabetes, HTN, Hep C and HIV are listed as "modifiable", not because they are curable per se, but can be controlled.
ART
Diabetes
= Modifiable
Hepatitis C
= Nonmodifiable
Gupta SK, et al. Clinical Infectious Disease ; 40:

16. IDSA Initial Evaluation Recommendations
Obtain baseline GFR:
All patients at the time of HIV diagnosis should be assessed for existing kidney disease with a screening urinalysis for proteinuria and a calculated estimate of renal function
Annual screening:
If there is no evidence of proteinuria at initial evaluation, patients at high risk for the development of proteinuric renal disease should undergo annual screening
Renal function should be estimated on a yearly basis to assess for changes over time
When to consider a nephrology consult:
Additional evaluations and referral to a nephrologist are recommended for patients with proteinuria of grade ≥1+ by dipstick analysis or GFR<60 mL/min per 1.73m2
Objective: That physicians follow guidelines to screen and monitor patients appropriately for kidney disease
Transition: On to the lipodystrophy section
Gupta SK, et al. Clinical Infectious Disease ; 40:

17. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 17

18. The Causation of Lipodystrophy Is Multi-Factorial in HIV Positive Patients
Objective: Development of lipodystrophy is multifactorial with host, viral and certain treatments contributing to fat redistribution.
Transition: The clinical significance of lipodystrophy is (listed on the next slide).

19. Potential Clinical Impact of Lipodystrophy
Morphological1
Quality of life
Patient adherence
Metabolic2
Insulin resistance
Impaired glucose tolerance
Type 2 diabetes
Hypertriglyceridemia
Hypercholesterolemia
Increased free fatty acids (FFA)
Decreased high density lipoprotein (HDL)
Objective: The downstream complications of lipodystrophy are more than just cosmetic effects
Transition: How can you avoid or manage lipodystrophy
1Falutz J., Nat Clin Pract Endocrinol Metab Sep;3(9):
2Behrens G, et al. Lipodystrophy syndrome. HIV Medicine. 15th ed Available at: Accessed September 25, 2008.

20. 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
Objective: Summary slide of a variety of options that should be considered when managing a patient with lipodystrophy
Transition: On to diabetes section
Falutz J., Nat Clin Pract Endocrinol Metab Sep;3(9):

21. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 21

22. 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:
Objective: HIV positive patients are at a higher risk for diabetes than the general population
Transition: How do we define insulin resistance, impaired glucose tolerance in diabetes
Certain ARVs
Older age
Ethnic background (African American)
Male sex
Greater BMI
1Florescu, D. Antiretroviral Therapy : Brown, TT. Arch Intern Med : DeWit, D. Diabetes Care (6):

23. Diabetes Diagnostic Criteria
Objective: To define IFG, IGT and DM.
Transition: Downstream effects of insulin resistance comprise
Florescu, D. Antiretroviral Therapy :

24. 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
Objective: Insulin resistance leads to more serious complications
Transition: How to screen for and manage insulin resistance
Florescu, D. Antiretroviral Therapy :

25. Diagnosis and Management of Insulin Resistance in HIV-Infected Patients
Fasting serum glucose measurement
• At baseline and 3-6 months after starting HAART
• Yearly thereafter
Oral glucose tolerance test
At the first visit in patients with family history of diabetes or obesity
Repeat when there is clinical suspicion of impaired glucose tolerance
Lifestyle modification
• Diabetic education
• Self-monitoring of blood glucose
• Aerobic and resistance training
Objective: Call to action of diagnosis and management of insulin resistance in HIV positive patients
Transition: On to the cardiovascular section
Florescu, D. Antiretroviral Therapy :

26. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 26

27. 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
Objective: Establish cardiovascular disease as an important comorbidity in HIV postive individuals
Transition: Show MI rates for HIV +/- individuals
D:A:D Study Group. The Lancet (9622):

28. MI Rates in HIV Positive and HIV Negative Patients
Age Group (Years)
Events per Person-Years 20 40 60 80
100
18-34
35-44
45-54
55-64
65-74
HIV+
HIV–
AMI rate by age group
Objective: As stated
Transition: There are a number of contributing factors to CV disease in HIV positive individuals
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:

29. 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
Objective: As stated
Transition: Utilize the guidelines to manage CV risk and lipid disorders
Viremia
Oxidative Stress
= HIV Infection
= ART
= HIV Infection & ART
Adapted from Dube M, et al. Circulation. 2008;118:e36-e40.

30. IDSA Guidelines: General Approach to CV Risk in HIV Positive Patients
Obtain fasting lipid profile, prior to starting antiretrovirals and within 3 to 6 months of starting new regimen
Count number of CHD risk factors and determine level of risk. If ≥2 risk factors, perform a 10-year risk calculation
Intervene for modifiable nonlipid risk factors, including diet and smoking
If above the lipid threshold based on risk group despite vigorous lifestyle interventions, consider altering antiretroviral therapy or lipid-lowering drugs
Objective: To follow current CV guidelines established for HIV positive patients.
Transition: How to calculate CV risk.
IF LIPID-LOWERING DRUGS ARE NECESSARY
Serum LDL cholesterol above threshold, or triglycerides mg/dL with elevated non-HDL cholesterol: STATINS
Serum triglycerides >500 mg/dL: FIBRATES OR
Dubé MP et al. Clin Infect Dis. 2003;37: IDSA = Infectious Diseases Society of America.

31. Calculating Framingham Risk
Objective: Calculate 10 year CV risk in all HIV positive patients at baseline
Transition: Conclusion
Available at: Accessed September 25, 2008.

32. Summary
Due to advances in HAART, HIV positive patients are growing older and living longer
HIV positive individuals may experience common comorbidities as they grow older
Renal dysfunction
Lipodystrophy
Insulin resistance / Diabetes
Cardiovascular disease
Comorbidities may be increasingly important in therapeutic decisions involving aging HIV positive patients

33. Comorbidities Associated With an Aging HIV Positive Population
I. Epidemiology
II. Introduction to Case Study
III. Comorbidities
Renal
Lipodystrophy
Insulin Resistance / Diabetes
Cardiovascular
IV. Case Study Facilitation 33

34. Case Study: Treatment-Experienced Patient
Patient is a 63-year-old African American man who presents to the office for routine follow-up
HIV positive for 6 years and has been on a BID boosted PI-based antiretroviral regimen since diagnosis
No history of prior treatment intolerance or virologic failures
He describes mild long-standing fatigue and infrequent episodes of diarrhea
Current labs:
CD4+ = 436 cells/mm3, VL <50 copies/mL,
WBC = 5.2 cells/μL, Hgb = 14.1g/dL, Platelet count = 236,000
TC = 212 mg/dL, TG = 190 mg/dL, LDL = 123 mg/dL, HDL = 41 mg/dL
FBG = 120mg/dl, Creatinine = 1.2 mg/dL, BUN = 6 mg/dL, Normal LFTs
eGFR (C-G method) = 78.8 mL/min/1.73 m2
Objective: Introduce a 63 y/o HIV patient who has slightly elevated risk for both cardiovascular disease and renal disease.
Transition to physical exam and reason for patient visit.

35. Case Study: Treatment-Experienced Patient
Current meds: ARV regimen, statin, PRN antidiarrheal
No history of diabetes, HTN, tobacco use, or family history of CAD
Physical exam: lipoatrophy of face, arms, and legs; Waist circumference = 39”
Patient is starting a new job and has concerns about his current ARV regimen
Objective: Complete medical history and describe patient visit to provider
Transition: Questions to consider for this patient.

36. Case Study: Treatment-Experienced Patient
How does this patient’s age affect your initial evaluation?
How do his physical exam and lab values factor into treatment decisions?
What are the similarities and differences in how you would manage this patient compared to a younger patient?