Cardiovascular Side Effects of HIV Treatment

1
Cardiovascular Side Effects of HIV Treatment

• Jean-Guy Baril, MD
• Mark Wainberg, Phd

2
The DAD Cohort

• What is DAD?
• The Data Collection on Adverse events of Anti-HIV
  Drugs (DAD)
• A prospective multi-cohort study of HIV-1
  positive persons under active follow up.
• DAD 1 23,441 patients enrolled 1999-2001
• DAD 2 12,900 patients enrolled through Spring
  2004
• DAD 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/de
fault.aspx
3

• MI incidence increases with longer exposure to
  combination antiretroviral therapy

Adjusted relative rate, 1.16 per year of
exposure 95 confidence interval CI,1.09 to
1.23
Myocardial Infarction Incidence per 1000
Person-year
Source Class of Antiretroviral Drugs and the
Risk of Myocardial Infarction. Writing committee
N Friis-Moller et al. N Engl J Med. 2007 April
263561723-35
4
MI Risk and Drug Class
Myocardial Infarction Adjusted Relative Rate
Source Class of Antiretroviral Drugs and the
Risk of Myocardial Infarction. Writing committee
N Friis-Moller et al. N Engl J Med. 2007 April
263561723-35
5
Increased risk of myocardial infarction after
cumulative exposure to HIV medications

• Cumulative exposure (relative rate RR per
  additional year)
• Indinavir 1.12 95 CI, 1.071.18
• Lopinavir-ritonavir 1.13 95 CI, 1.051.21
• Abacavir 1.07 95 CI, 1.001.14
• Recent Exposure to
• abacavir 1.70 95 CI, 1.172.47
• didanosine RR,1.41 95 CI, 1.091.82

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 (DAD) Study. Worm SW et al. J
Infect Dis. 2010 Feb 1201(3)318-30.
6
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
7
DAD Risk for Current or Recent Exposure to
Abacavir

• Relative Rate
• 1.70 95 CI, 1.172.47

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 (DAD) Study. Worm SW
et al. J Infect Dis. 2010 Feb 1201(3)318-30.
8
DAD Risk for Cumulative Exposure to Abacavir

• Relative Rate of MI per Additional year
• 1.07 95 CI, 1.001.14

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 (DAD) Study. Worm SW
et al. J Infect Dis. 2010 Feb 1201(3)318-30.
9
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 157(3)245-53.
10
Lack of CVD Risk with Atazanavir
Source Monforte A. dA. et al. ATV-containing
ART Is Not Associated with an Increased Risk
of Cardio- or Cerebro-vascular Events in the
DAD Study . CROI 2012 Paper 823
11
No Effect from Ritonavir Boosting
Source Monforte A. dA. et al. ATV-containing
ART Is Not Associated with an Increased Risk
of Cardio- or Cerebro-vascular Events in the
DAD Study . CROI 2012 Paper 823
12
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 May55(5)800-4
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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
263561723-35
14
Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD Incidence rate ratio per year of exposure to ARVs on risk of CKD
Univariate Univariate Univariate Multivariate Multivariate Multivariate
IRR (/year) 95 CI p IRR (/year) 95 CI p
Tenofovir 1.32 1.21-1.41 lt0.0001 1.16 1.06-1.25 lt0.0001
Indinavir 1.18 1.13-1.24 lt0.0001 1.12 1.06-1.18 lt0.0001
Atazanavir 1.48 1.35-1.62 lt0.0001 1.21 1.09-1.34 0.0003
Lopinavir 1.15 1.07-1.23 lt0.0001 1.08 1.01-1.16 0.030
CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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. CKD, confirmed (persisting for gt3 months) decrease in eGFR lt60 mL/min/1.73m2 if eGFR at baseline gt60 mL/min/1.73m2 or confirmed 25 decrease in eGFR if baseline eGFR lt80 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