cardiovascular side effects of hiv treatment jean-guy baril, md mark wainberg, phd
TRANSCRIPT
Cardiovascular Side Effects of HIV Treatment
Jean-Guy Baril, MDMark 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
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
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Adjusted relative rate, 1.16 per year of exposure; 95% confidence interval [CI],1.09 to 1.23
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
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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 SpecificIndividual Antiretroviral Drugs from the 3 Major Drug classes: The Data Collection onAdverse 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 IndividualAntiretroviral Drugs from the 3 Major Drug classes: The Data Collection on Adverse Events ofAnti-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 IndividualAntiretroviral Drugs from the 3 Major Drug classes: The Data Collection on Adverse Events ofAnti-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 ofacute myocardial infarction: a cohort and nested case-control study using Québec's publichealth 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 ofCardio- 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 ofCardio- 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 withlopinavir/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-termFollow-up: The EuroSIDA Study Paper # 107LB