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

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Presentation on theme: "Cardiovascular Side Effects of HIV Treatment Jean-Guy Baril, MD Mark Wainberg, Phd."— Presentation transcript:

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? –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 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 MI incidence increases with longer exposure to combination antiretroviral therapy 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: 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

4 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 April 26;356: Myocardial Infarction Adjusted Relative Rate

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. dA. 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. dA. 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 UnivariateMultivariate IRR (/year) 95% CIpIRR (/year) 95% CIp Tenofovir < < Indinavir < < Atazanavir < Lopinavir < CKD, confirmed (persisting for >3 months) decrease in eGFR 60 mL/min/1.73m 2 or confirmed 25% decrease in eGFR if baseline eGFR <80 mL/min/1.73m 2. 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


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