Transcript Kidney Disease in HIV Positive Patients

Comorbidities in an
Aging HIV Positive
Population
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
Prevalence (%)
50
GFR (mL/min/1.73 m2):
40
45
45-59
30-44
<30
N = 65,605
30
20
10
0
20-29
30-39
40-49
50-59
60-69
Age (Years)
Adapted from Hallan SI, et al. BMJ. 2006; 333:1047-1050.
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
2Gupta
SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.
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
Ethnicity
Family
History
Age
HIV
CKD
Risk
ART
= Modifiable
= Nonmodifiable
Hypertension
Diabetes
Hepatitis C
Gupta SK, et al. Clinical Infectious Disease. 2005; 40:1559-1585.
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 MultiFactorial 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 era1
• Diabetes in HIV positive men with HAART exposure > 4X
HIV-seronegative men2
• Risk factors for HIV positive individuals developing
diabetes include3:
• Certain ARVs
• Older age
• Ethnic background (African American)
1Florescu,
D. Antiretroviral Therapy. 2007. 12:149-162.
TT. Arch Intern Med. 2005. 165:1179-1184.
3DeWit, D. Diabetes Care. 2008. 31(6):1224-1229.
2Brown,
• Male sex
• Greater BMI
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
White race
Family history
Secondary
Decreased physical
activity
Alcohol
Decreased bone
acquisition
Increasing age
Chronic diseases
(e.g. hyperthyroidism, hyperparathyroidism,
liver disease, rheumatological conditions,
eating disorders, etc.)
Hypogonadism
Renal dysfunction
Malnutrition/low BMI
Amenorrhoea
/premature menopause
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)
Gender-adjusted rates of fracture
among adults aged 25-54 years
HOPS
P value for trend = 0.01
– Adjusted for age and gender
• HOPS: 276 fx during median 4.8
yrs follow-up; more likely if:
• Age >47
NHAMCSOPD
P value for trend = 0.32
• Nadir CD4+ count <200
• HCV co-infection
• Diabetes
• Substance use
• Conclusion: Fracture rates are
Dao C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 128.
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
Events per
1000 Person-Years
100
HIV+
80
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
Insulin
Resistance
Viremia
= HIV Infection
= HIV Infection & ART
Adapted from Dube M, et al. Circulation. 2008;118:e36-e40.
Oxidative Stress
Prediction of cardiovascular risk based on
the Framingham Heart Study
Risk Factor
Units
Gender
Age
Total Cholesterol
HDL
Systolic Blood Pressure
Treatment for Hypertension (Only if SBP >120)
Current Smoker
male or female
years
mg/dL
mg/dL
mmHg
yes or no
yes or no
m
46
245
35
125
n
n
10 years
10
0,06
6%
Time Frame for Risk Estimate
Your Risk
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
Units
Gender
Age
Total Cholesterol
HDL
Systolic Blood Pressure
Treatment for Hypertension (Only if SBP >120)
Current Smoker
male or female
years
mg/dL
mg/dL
mmHg
yes or no
yes or no
m
46
245
35
125
n
y
10 years
10
Time Frame for Risk Estimate
0,19
Your Risk
0,00
0,05
0,10
0,15
http://hin.nhlbi.nih.gov/atpiii/calculator.asp
0,20
19%
0,25
0,30