HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

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HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients Roger Bedimo, MD; Henning Drechsler, MD; Song Zhang, PhD; Andrew Westfall, MS; Naim Maalouf, MD

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HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients. Roger Bedimo, MD; Henning Drechsler, MD; Song Zhang, PhD; Andrew Westfall, MS; Naim Maalouf, MD. Osteoporotic Fractures among HIV-Infected Patients: Incidence. - PowerPoint PPT Presentation

Transcript of HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Page 1: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures

Among HIV Patients

Roger Bedimo, MD; Henning Drechsler, MD; Song Zhang, PhD; Andrew Westfall, MS; Naim Maalouf, MD

Page 2: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Osteoporotic Fractures among HIV-Infected Patients: Incidence

Decreased bone mineral density is increasingly reported in the aging HIV-positive population. Interaction b/w low BMD and bone turnover in

predicting fracture risk1

15-30% of HIV-infected patients are co-infected with hepatitis C, which by itself is associated with osteoporosis and bone turnover2

The aging of the HIV population suggests that fracture risk will increase in HAART vs. pre-HAART era.

1Gamero. J Bone Miner Res 1996,11:1531-1538; 2Gastroenterology 2003,125:937-940

Page 3: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Osteoporotic Fractures among HIV-Infected Patients: Mortality

Fracture prevalence is increased in HIV-infected compared with non-HIV-infected patients.1

The HIV population in the US is predominantly male.

Although the overall prevalence of fragility fractures is higher in women, men generally have higher rates of fracture-related mortality.

2,3 The overall mortality is about 20% in the first 12

months after hip fracture and is higher in men than women

2Center JR, et al. Lancet 1999; 353:878; 3Hasserius R, et al.. Osteoporos Int 2003;14:61.

1Triant V, et al., JCEM 2008;93: 3499–3504;

Page 4: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Factors Likely Associated with Decreased Bone Health in HIV

OSTEOPOROSIS and

­ FRACTURE RISK

Inflammatory Cytokines

HIV HAART

Hypogonadism

Glucocorticoids

HCV

Malnutrition, low BMI

Tobacco, Alcohol

Vitamin D deficienc

y

Chronic kidney disease

Aims: To evaluate the impact of HCV co-infection on the

risk of osteoporotic fractures among HIV-infected patients.

To evaluate the impact of osteoporotic fractures on all-cause mortality

Page 5: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Methods: Data Source, Predictors and Outcome Measures

• Data Source: Veterans Affairs’ Clinical Case Registry; HIV patients in pre-HAART (’88-’95) and HAART eras (’96-’09).

• Predictors: – HCV co-infection: ICD-9 codes for HCV or HCV

antibody +

– Chronic kidney disease: Estimated GFR<60 by MDRD

– BMI, Age, Race, Antiretroviral exposure, Smoking

• Outcomes: – Osteoporotic fractures: Vertebral fractures (ICD-9

codes 805.2 through 805.7), Hip fractures (820.0 through 820.9), and Wrist fractures (814.0, 814.1, 813.4 and 813.5)

– All-cause mortality: Cox survival model

Page 6: HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients

Results: Study Population, Treatment Exposure and

Events• Patients: 56,660 included in the analysis; 98.1%

male; 17,281 (31.2%) HCV+; Mean age at entry: 45.0 (SD:10.4)

• Follow-up: 305,237 patient-years; mean: 5.4 yrs/patient (range: 0 – 23.8 years)

• ARV exposure: 64.2% of patients exposed for ≥ 30 days. Mean Rx duration: 4.08 years (range: 0 – 18.7; SD: 3.92).

• Osteoporotic fractures during period of observation: – 951 individual patients sustained at least one

osteoporotic fracture (106 vertebral, 451 wrist and 308 hip).

– Rate/1000 patient-years for HIV and HIV/HCV patients were 2.54 and 3.25 respectively.

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Risk Factors among Patients with and without Osteoporotic

FractureTotal

(n =56,660)

Fracture (n =951)

No Fracture(n =55,709)

P-value

Age in Yrs; mean (SD)

45.01 (10.36) 47.48 (10.08)

44.97 (10.36) P<0.0001

% Male 98.05 97.91 98.05 P=0.91

% Whites 45.14 57.10 44.83 P<0.0001

% with Tobacco Use

32.85 56.47 32.39 P<0.0001

% Diabetes 15.28 24.86 15.10 P<0.0001

% BMI<20 33.24 48.81 32.88 P<0.0001

% HCV Positive 31.40 50.5 31.02 P<0.0001

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Age-adjusted Rates of Osteoporotic Fractures (Entire Cohort)

0

1

2

3

4

5

6

7

8

18-29 30-39 40-49 50-59 60-69 ≥70

Age at Diagnosis (Years)

Fra

ctu

re R

ate

(p

er

1,0

00

pati

en

t-years

)

Vertebral

Hip

Wrist

Total

General population1

1Data from Triant V, et al., JCEM 2008;93: 3499–3504

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Rates of Osteoporotic Fractures by Year of Diagnosis and HCV

Status

88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09.00

1.00

2.00

3.00

4.00

5.00

6.00

HIV Patients HIV/HCV Patients

Year of Diagnosis

Fra

ctu

re R

ate

/10

00

PY

rs

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Factors Predicting Osteoporotic Fracture in HIV Patients

Factors Hazard Ratio (95% Confidence Interval; p value)

  Univariate Analysis Multi-variable Analysis

HCV Co-infection 1.27 (1.11 - 1.44; p = 0.0003)

1.43 (1.22 - 1.69; p< 0.0001)

CKD (eGFR <60) 1.34 (1.03 – 1.74; p=0.03) 1.10 (0.77 – 1.58; p = 0.61)

White Race 1.64 (1.41 – 1.89; p < 0.0001)

1.75 (1.49 – 2.04; p< 0.0001)

Age (per 10 year increase)

1.49 (1.40 – 1.59; p <0.0001)

1.50 (1.38 – 1.63; p< 0.0001)

ART Use 0.57 (0.48 – 0.67; p<0.0001)

0.44 (0.35 – 0.56; p<0.0001)

Tobacco Use 1.30 (1.14 – 1.48; p<0.0001)

1.48 (1.26 – 1.75; p<0.0001)

Diabetes 1.18 (1.02 – 1.37; p=0.02) 1.02 (0.85 – 1.22; p=0.85)

BMI < 20 1.54 (1.29 – 1.82; p<0.0001)

1.40 (1.13 – 1.73; p=0.002)

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Fracture Rates in HIV and HIV/HCV Patients

HIV HIV/HCV HIV HIV/HCVHAART Era ('96-'09): 258,326

PYEntire Period ('88-'09): 303,678

PY

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

2.86

4.06

2.54

3.35

Fracture Rate/1000 PY

Fra

ctu

re R

ate

(p

er

1,0

00

pati

en

t-years

)

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Predictors of Death of Patients with HIV in the HAART era

Factors Hazard Ratio (95% Confidence Interval; p value)

  Univariate Analysis Multi-variable Analysis

Osteoporotic Fracture

2.29 (2.05 – 2.56; p<0.0001)

1.77 (1.52 – 2.06; p<0.001)

HCV Co-infection 1.12 (1.08 – 1.16; p<0.0001)

1.41 (1.32 - 1.50; p<0.0001)

CKD (eGFR <60) 1.89 (1.39 – 2.56; p<0.0001)

2.17 (1.96 – 2.41; p < 0.0001)

Black Race 1.16 (1.10 – 1.22; p<0.0001)

1.12 (1.05 – 1.19; p=0.0003)

Age (per 10 year increase)

1.40 (1.37 – 1.42; p<0.0001)

1.60 (1.55 – 1.65; p < 0.0001)

ART Use 0.46 (0.44 – 0.48; p<0.0001)

0.50 (0.45 – 0.54; p< 0.0001)

Diabetes 0.89 (0.85 – 0.93; p<0.0001) 1.04 (0.97 – 1.11; p=0.28)

BMI<20 2.55 (2.44 – 2.67; p<0.0001)

2.27 (2.12 – 2.44; p<0.0001)

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Discussion - I

• HCV co-infection is associated with a higher risk of osteoporotic fractures among HIV-infected patients.

• Risk of osteoporotic fractures appears to be increasing in the HAART era among HIV/HCV patients.

• Exposure to antiretroviral therapy appears to be protective of osteoporotic fractures. – Higher overall mortality in the pre-HAART era might

not have allowed time to develop osteoporotic fractures

– It is possible that HAART is not protective, but a surrogate measure of patients with better care

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Discussion - II

• Patients with HIV have a higher incidence of fractures than the general population, in spite of HAART therapy which may reduce fracture risk

• Other factors associated with increased risk of osteoporotic fractures include White race, advancing age and smoking.

• CKD and diabetes were not associated with osteoporotic fracture

• Osteoporotic fracture is an independent predictor of all-cause mortality.

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Strengths and Limitations

• Our study is a retrospective cohort study.

• Large sample size (more than 56,000 patients; more than 900 with fracture events)

• Uniform data collection on exposures and outcomes across VA system, including pre-HAART and HAART eras.

• Osteoporotic fracture events not ascertained (only ICD-9 code used – validated in other VA studies)

• Bone mineral density is not evaluated. Fractures cannot be proven to be osteoporotic in nature.

• Impact of type (HAART and non-HAART) and duration of antiretroviral exposure not completed (in progress)

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Acknowledgements

• VA Center for Quality Management for access to CCR data and material support

• Dr. Pablo Tebas for great insight, critical review and comments

• IAS for giving us the opportunity to share our work