comorbidities in an aging hiv positive population fernando garcia, md valley aids council...

Comorbidities in an Aging HIV Positive Population

Fernando Garcia, MD

Valley AIDS Council

HalingenTExas

Comorbidities Associated With anAging HIV Positive Population

I. Epidemiology

II. Introduction to Case Study

III. Comorbidities

• Renal

• Lipodystrophy

• Insulin Resistance / Diabetes

• Cardiovascular

IV. Case Study Facilitation

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

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: http://aging.senate.gov/events/hr141gs.pdf. Accessed September 25, 2008.

Age Distribution (in years) of HIV Positive Individuals Living in the United States

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

100,000

110,000

<13 13-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 >65

Age Group (Years)

Es

tim

ate

d N

um

be

r o

f P

ers

on

s L

ivin

g w

ith

HIV

/AID

S

2003

2006

Adapted from CDC Surveillance Report 2006

Rate of HIV Related Deaths Have Declined Since 1999

Sackoff JE, et al. Ann Interm Med. 2006;145:397-406.

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

Rat

e p

er 1

0,00

0 p

ers

on

s w

ith

AID

S

Age-adjusted AIDS mortality rate by underlying cause of death

• 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

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

1Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585., 2Falutz J., Nat Clin Pract Endocrinol Metab. 2007 Sep;3(9):651-61. 3Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.4Schambelan M et al. Circulation. 2008;118:e48-e53.


I. Epidemiology


III. Comorbidities

• Renal

• Lipodystrophy


• Cardiovascular


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


• 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


• 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?


I. Epidemiology


III. Comorbidities

• Renal

• Lipodystrophy


• 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.

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

Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.


I. Epidemiology


III. Comorbidities• Renal

• Lipodystrophy


• Cardiovascular


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.

The Causation of Lipodystrophy Is Multi-Factorial in HIV Positive Patients

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)

1Falutz J., Nat Clin Pract Endocrinol Metab. 2007 Sep;3(9):651-61.

2Behrens G, et al. Lipodystrophy syndrome. HIV Medicine. 15th ed. 2007. Available at: http://www.hivmedicine.com/hivmedicine2007.pdf. Accessed September 25, 2008.

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.


I. Epidemiology


III. Comorbidities

• Renal

• Lipodystrophy


• 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)

Diabetes Diagnostic Criteria

Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.

Test Criteria

Fasting plasma glucose≥ 126 mg/dL (≥ 6.99 mmol/L), confirmed by

repeat testing or

OGTTPlasma glucose 2 hours after 75 g oral glucose ≥ 200 mg/dL (≥ 11.10 mmol/L)

Random plasma glucose≥ 200 mg/dL (≥ 11.10 mmol/L) with polyuria

and polydipsia

Test Criteria

Fasting plasma glucose≥ 126 mg/dL (≥ 6.99 mmol/L), confirmed by

repeat testing or

OGTTPlasma glucose 2 hours after 75 g oral glucose ≥ 200 mg/dL (≥ 11.10 mmol/L)

Random plasma glucose≥ 200 mg/dL (≥ 11.10 mmol/L) with polyuria

and polydipsia

Test Criteria

Fasting plasma glucose ≥ 126 mg/dL, confirmed by repeat testing or

Oral Glucose Tolerance TestPlasma glucose 2 hours after 75 g oral

glucose ≥ 200 mg/dL

Random plasma glucose ≥ 200 mg/dL with polyuria and polydipsia

Test Criteria

Fasting plasma glucose ≥ 126 mg/dL, confirmed by repeat testing or

Oral Glucose Tolerance TestPlasma glucose 2 hours after 75 g oral

glucose ≥ 200 mg/dL

Random plasma glucose ≥ 200 mg/dL with polyuria and polydipsia

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

Florescu, D. Antiretroviral Therapy. 2007. 12:149-162.

Diagnosis and Management of InsulinResistance 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 trainingFlorescu, D. Antiretroviral Therapy. 2007. 12:149-162.


I. Epidemiology


III. Comorbidities

• Renal

• Lipodystrophy


• 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

IDSA Guidelines: General Approach to CV Risk in HIV Positive Patients

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

IF LIPID-LOWERING DRUGS ARE NECESSARY

OR

Serum LDL cholesterol above threshold, or triglycerides 200-500 mg/dL

with elevated non-HDL cholesterol: STATINS

Serum triglycerides >500 mg/dL:FIBRATES

Obtain fasting lipid profile, prior to starting antiretrovirals and within 3 to 6 months of starting new regimen

Dubé MP et al. Clin Infect Dis. 2003;37:613-627. IDSA = Infectious Diseases Society of America.

Calculating Framingham Risk

Available at: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof. Accessed September 25, 2008.

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


I. Epidemiology


III. Comorbidities

• Renal

• Lipodystrophy


• Cardiovascular



• 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


• 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


• 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?

comorbidities in an aging hiv positive population fernando garcia, md valley aids council...

Documents

hiv positive patients

rate of hiv related

routine followup hiv

nonhiv related causes

case study facilitation

aging patient population

vl slide

current arv regimen