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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.
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
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
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
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?
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
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.
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
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.
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
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.
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
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
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
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
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
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?
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