1. Cardiovascular Side Effects of HIV Treatment
Jean-Guy Baril, MD
Mark Wainberg, Phd

2. The D:A:D Cohort What is D:A:D? 11 cohorts worldwide
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
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:

3. Incidence per 1000 Person-year Myocardial Infarction
MI incidence increases with longer exposure to combination antiretroviral therapy
Adjusted relative rate, per year of exposure;
95% confidence interval [CI],1.09 to 1.23
Incidence per 1000 Person-year
Myocardial Infarction
Source: Class of Antiretroviral Drugs and the Risk of Myocardial Infarction.
Writing committee: N Friis-Moller et al. N Engl J Med April 26;356:

4. Myocardial Infarction Adjusted Relative Rate
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 April 26;356:

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, 1.07–1.18]
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 Feb 1;201(3):

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. 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 Feb 1;201(3):

8. 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 Feb 1;201(3):

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 Jul 1;57(3):

10. 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

11. 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

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 May;55(5):800-4

13. 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 April 26;356:

14. Incidence rate ratio per year of exposure to ARVs on risk of CKD
Univariate
Multivariate
IRR
(/year)
95% CI p
Tenofovir
1.32
<0.0001
1.16
Indinavir
1.18
1.12
Atazanavir
1.48
1.21
0.0003
Lopinavir
1.15
1.08
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 Chronic Kidney Disease and Exposure to ART in a Large Cohort with Long-term
Follow-up: The EuroSIDA Study Paper # 107LB