Transcript Ask The Expert Cardiovascular Side Effects of HIV Treatment

Cardiovascular Side Effects of HIV
Treatment
Jean-Guy Baril, MD
Mark Wainberg, Phd
The D:A:D Cohort
• What is D:A:D?
– The Data Collection on Adverse events of Anti-HIV Drugs (D:A:D)
– A prospective multi-cohort study of HIV-1 positive persons under active follow
up.
• D:A:D 1 – 23,441 patients enrolled 1999-2001
• D:A:D 2 – 12,900 patients enrolled through Spring 2004
• D:A:D 3 – 16,000 patients enrolled in 2010
• 11 cohorts worldwide
• More than 49,000 patients from 212 clinics in 33 countries in Europe, USA
and Australia.
• Core Data:
– Incident cases of cardiovascular disease in HIV infected persons
• Other Data:
– Risk factors for CVD including previous MI, stroke, family history, smoking
status, diabetes, dyslipidemia, and hypertension
– Investigate associations between these risk factors, stage of HIV disease and
use of antiretroviral therapies
– Non-AIDS defining malignancies
– End-stage renal disease
– Chronic liver disease
– Death
Source: http://www.cphiv.dk/dad/about/tabid/106/default.aspx
MI incidence increases with longer
exposure to combination antiretroviral
therapy
Myocardial Infarction
Incidence per 1000 Person-year
Adjusted relative rate, 1.16 per year of exposure;
95% confidence interval [CI],1.09 to 1.23
Source: Class of Antiretroviral Drugs and the Risk of Myocardial Infarction.
Writing committee: N Friis-Moller et al. N Engl J Med. 2007 April 26;356:1723-35
Myocardial Infarction
Adjusted Relative Rate
MI Risk and Drug Class
Source: Class of Antiretroviral Drugs and the Risk of Myocardial Infarction.
Writing committee: N Friis-Moller et al. N Engl J Med. 2007 April 26;356:1723-35
Increased risk of myocardial infarction after
cumulative exposure to HIV medications
• Cumulative exposure (relative rate [RR] per additional year)
– Indinavir 1.12 [95% CI, 1.07–1.18]
– Lopinavir-ritonavir 1.13 [95% CI, 1.05–1.21]
– Abacavir 1.07 [95% CI, 1.00–1.14]
• Recent Exposure to
– abacavir 1.70 [95% CI, 1.17–2.47]
– didanosine RR,1.41 [95% CI, 1.09–1.82]
Source: Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific
Individual Antiretroviral Drugs from the 3 Major Drug classes: The Data Collection on
Adverse Events of Anti-HIV Drugs (D:A:D) Study.
Worm SW et al. J Infect Dis. 2010 Feb 1;201(3):318-30.
FDA Meta-Analysis of CVD Risk from
Abacavir Containing Regimens
Source: Ding X., et al. No Association of Myocardial Infarction with ABC Use:
An FDA Meta-analysis . CROI 2011 Paper #808
D:A:D Risk for Current or Recent
Exposure to Abacavir
• Relative Rate
– 1.70 [95% CI, 1.17–2.47]
Source: Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific Individual
Antiretroviral Drugs from the 3 Major Drug classes: The Data Collection on Adverse Events of
Anti-HIV Drugs (D:A:D) Study. Worm SW et al. J Infect Dis. 2010 Feb 1;201(3):318-30.
D:A:D Risk for
Cumulative Exposure to Abacavir
• Relative Rate of MI per Additional year
– 1.07 [95% CI, 1.00–1.14]
Source: Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific Individual
Antiretroviral Drugs from the 3 Major Drug classes: The Data Collection on Adverse Events of
Anti-HIV Drugs (D:A:D) Study. Worm SW et al. J Infect Dis. 2010 Feb 1;201(3):318-30.
Abacavir Associated MI Risk in the
Quebec Cohort
Source: Durand M et al. Association between HIV infection, antiretroviral therapy, and risk of
acute myocardial infarction: a cohort and nested case-control study using Québec's public
health insurance database. J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):245-53.
Lack of CVD Risk with Atazanavir
Source: Monforte A. d’A. et al. ATV-containing ART Is Not Associated with an Increased Risk of
Cardio- or Cerebro-vascular Events in the D:A:D Study . CROI 2012 Paper #823
No Effect from Ritonavir Boosting
Source: Monforte A. d’A. et al. ATV-containing ART Is Not Associated with an Increased Risk of
Cardio- or Cerebro-vascular Events in the D:A:D Study . CROI 2012 Paper #823
Effect of Lopinavir on Lipid Levels
Source: Montes ML, et al. Lipid disorders in antiretroviral-naive patients treated with
lopinavir/ritonavir-based HAART: frequency, characterization and risk factors.
J Antimicrob Chemother. 2005 May;55(5):800-4
MI Risk with Protease Inhibitor Use
• Unadjusted Relative Rate Per Year of
Exposure
– 1.16 (95% CI, 1.09 to 1.23)
• Adjusted for Lipid Levels
– 1.10 (95% CI, 1.04 to 1.18)
Source: Class of Antiretroviral Drugs and the Risk of Myocardial Infarction.
Writing committee: N Friis-Moller et al. N Engl J Med. 2007 April 26;356:1723-35
Incidence rate ratio per year of exposure to ARVs on risk of CKD
Univariate
Multivariate
IRR
(/year)
95% CI
p
IRR
(/year)
95% CI
p
Tenofovir
1.32
1.21-1.41
<0.0001
1.16
1.06-1.25
<0.0001
Indinavir
1.18
1.13-1.24
<0.0001
1.12
1.06-1.18
<0.0001
Atazanavir
1.48
1.35-1.62
<0.0001
1.21
1.09-1.34
0.0003
Lopinavir
1.15
1.07-1.23
<0.0001
1.08
1.01-1.16
0.030
CKD, confirmed (persisting for >3 months) decrease in eGFR <60 mL/min/1.73m2 if eGFR at baseline >60 mL/min/1.73m2 or confirmed 25%
decrease in eGFR if baseline eGFR <80 mL/min/1.73m2. Adjusted for eGFR baseline, AIDS at baseline, AIDS during follow up, use of nephrotoxic
drugs, current CD4, current age, current HIV viral load. Any CV event (stroke, acute MI, bypass, angioplasty or carotid endarterectomy),
hypertension, diabetes, hepatitis C status, non-AIDS malignancy, and gender. Variable included as time-updated. No other ARVs or types of
antiretroviral regimen were significantly associated with CDK.
Ole Kirk et al. 2010 Chronic Kidney Disease and Exposure to ART in a Large Cohort with Long-term
Follow-up: The EuroSIDA Study Paper # 107LB