Cardiovascular Complications of HIV
Mark Boyd MD, FRACP
The Kirby Institute
for infection and immunity in society
7th IAS Conference Kuala Lumpur, Malaysia
03 July 2013
Cardiovascular Complications of HIV
Conflicts of interest
Grants
Honoraria
AbbVie
AbbVie
Gilead Sciences
Boehringer-Ingelheim
Merck
Bristol Myers Squibb
Janssen-Cilag
Merck
Cardiovascular Complications of HIV
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Cardiovascular Complications of HIV
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Myocardial Infarction rates in HIV+ versus HIVMean MI rate = 11 v 7
per 1000 person years
RR=1.7
Triant J, et al. Clin Endocrinol Metab. 2007.
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Risk factors CVD HIV+ vs HIVHIV-neg men
HIV-pos men
HIV-neg women
HIV-pos. women
Dyslipidaemia
Smoking
Insulin
resistance
Kaplan R, et al. CID 2007.
Comorbidity distribution
*
Schouten J et al. World AIDS Conference July 2012;
updated May 2013 (personal communication, Reiss P)
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
SMART - major CVD, hepatic or renal disease
Endpoints
Relative risk
(95% CI)
No. of patients
with events
1.7
Major CVD, hepatic
or renal disease
104
CVD, fatal or non-fatal
79
Hepatic disease, fatal
or non-fatal
Renal disease, fatal
or non-fatal
1.6
1.4
17
4.5
11
0.1
►
El-Sadr W, et al. SMART. NEJM 2006
Favours DC
1
10
Favours VS ►
Cardiovascular complications of HIV
SMART: risk of death strongly associated with
IL-6 & D-dimer biomarker levels at study entry
Biomarker
<25th
percentile
(reference)
25th-49th
percentile
50th-74th
percentile
>75th
percentile
OR
(95%CI)
OR
(95t% CI)
OR
(95% CI)
p-value
IL-6
(inflammation)
1.0
1.5
(0.7-3.1)
3.2
(1.3-7.9)
8.3
(3.3-20.8)
<0.0001
D-dimer
(coagulation)
1.0
3.2
(1.1-9.0)
4.0
(1.3-12.3)
12.4
(4.3-37.0)
<0.0001
Kuller L, et al. PLoS Med 2008
Untreated HIV infection and
CVD pathogenesis: a proposed model
Baker J and Lundgren J. Eur Heart J 2011
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Cardiovascular complications of HIV
ART and myocardial infarction
MI incidence according to duration of ART exposure
Friis-Moller N, et al. D:A:D. NEJM 2003.
Cardiovascular complications of HIV
MI risk disease by ARV exposure in D:A:D
ART exposure and MI risk in
D:A:D
Worm S, et al. D:A:D. JID 2012.
Untreated HIV infection and
CVD pathogenesis: a proposed model
Baker J and Lundgren J. Eur Heart J 2011
Treated HIV infection and
CVD pathogenesis: a proposed model
ART
Baker J and Lundgren Eur Heart J. 2011
Insulin resistance
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Stop Smoking
Myocardial Infarction
3.73
5-
3.40
3.00 2.62
2.07
1.73
IRR
1Baseline status
Never smoked Previous Current
0.5 -
Stopped smoking during follow-up
< 1 yr 1-2 yrs 2-3 yrs 3+ yrs
Adjusted for: age, sex, cohort, calendar year, antiretroviral treatment, family history of
CVD, diabetes, and time-updated lipids and blood pressure assessments
D:A:D study group. HIV Med 2011.
Cardiovascular disease in HIV
Prevention: monitor and modify risks
5
6
CVD hazard in D:A:D*
Reduce sysBP 10 mmHg
4
Reduce TC 1 mmol/L
1
2
3
Stop smoking
40
45
50
55
60
65
age
*relative to 40 y.o. HIV+ male
Petoumenos K for D:A:D . 20th CROI 2013.
Control dyslipidaemia: use TDF
TDF
(n=170)
Total-cholesterol (mmol/L) +0.78
HDL-cholesterol (mmol/L)
+0.23
LCL-cholesterol (mmol/L)
+0.36
TG (mmol/L)
+0.01
Total limb fat gain-DXA (kg) +8.6
Total weight gain (kg)
+2.9
Neuropathy
3%
d4T
(n=162)
+1.50
+0.16
+0.67
+1.51
+4.5
+0.6
10%
p-value
<0.001
0.003
<0.001
<0.001
<0.001
0.001
<0.001
Gallant J, et al. GS 934 study. JAMA 2004;292:191-201.
CVD complications of HIV
Prevention: adopt a healthy lifestyle
Score 0
Score 2
Score 3 & 4
Probability of CHD according to health score
Ahmed H et al. MESA. Am J Epi 2013.
CVD complications of HIV
Prevention: adopt a healthy lifestyle
Score 3 & 4
Score 2
Score 1
Score 0
Probability of death according to health score
Ahmed A, et al. MESA. Am J Epi 2013.
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
CVD complications of HIV: key messages
ART saves lives
Walker S, et al. DART. Lancet 2009.
CVD complications of HIV: key messages
The risk of death from AMI is much less than
the risk of dying from untreated HIV-infection
3 year risk
AIDS/Death
AMI
Off ART
23 - 29%
0.3%
(0.2-0.38)
On ART
6 - 11%
1%
(0.43-1.77)
Law M et al. HIV Med 2003.
CVD complications of HIV: key messages
Monitor and treat modifiable risk factors
•
•
•
•
•
Stop smoking
Monitor& treat hypertension
Monitor & treat dyslipidaemia and diabetes
Encourage healthy weight, diet and exercise
Monitor and treat HIV-infection
– according to guidelines
– there is no evidence to support use of specific ART
regimens for PLHIV with high-risk for CVD
Cardiovascular Complications
Outline
• Epidemiology
• Risk factors
– host
– virus-host
– ART
• Prevention
• Key messages
• Conclusions
Cardiovascular Complications of HIV
Conclusions
• Cardiovascular disease pathogenesis in HIV
is complex
• While HIV factors may add to complexity,
conventional risk factors are prominent
• Risks can be monitored and modified
• Primary prevention is key in low-, middleand high-income settings