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Massimo Galli DISC L.Sacco , Università di Milano Sezione di Malattie Infettive

Terapia antiretrovirale , alterazioni metaboliche e rischio cardiovascolare. Massimo Galli DISC L.Sacco , Università di Milano Sezione di Malattie Infettive. Scomode evidenze…. Il rischio cardiovascolare aumenta in relazione al tempo di esposizione ai PI boosted

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Massimo Galli DISC L.Sacco , Università di Milano Sezione di Malattie Infettive

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  1. Terapia antiretrovirale, alterazioni metaboliche e rischio cardiovascolare Massimo Galli DISC L.Sacco, Università di Milano Sezione di Malattie Infettive

  2. Scomode evidenze… • Il rischio cardiovascolare aumenta in relazione al tempo di esposizione ai PI boosted • Gli NRTI sono gravati da varie tossicità di classe o imputabili alle singole molecole, che hanno comportato restrizioni delle opzioni terapeutiche nei portatori di fattori di rischio cardiovascolare • L’EFV potrebbe contribuire a dare tossicità metabolica Leonado da Vinci, La battaglia di Anghiari (1503)

  3. ARTEMIS: change in median lipid levels up to Week 96 LPV/r baseline NCEP cut-off DRV/r baseline DRV/r Week 96 LPV/r Week 96 193 2.3 5.2 200 200 182 161 156 158 1.7 150 150 3.9 123 105 106 105 105 91 89 Median concentration 2.6 100 1.1 100 53 48 43 44 50 0.6 50 1.3 0 0 0 0 Total cholesterol LDL calculated HDL Triglycerides Left axis mg/dL; right axis mmol/mL Baraldi E, et al. IAS 2009. MOPEB034

  4. ALTAIR: TDF/FTC+ EFV or ATV/r or ZDV/ABC Metabolic Outcomes Mean Change in Metabolic Parameters at 48 Weeks mg/dL EFV vs ATV/r p=0.006 p=0.62 p=0.23 p<0.001 EFV vs ZDV/ABC p<0.01 p=0.013 p<0.001 p=0.03 Cooper D et al. IAS 2009 LBPEB09

  5. Low/stable rate of CVD as a cause of death in HIV-infected patients Proportion (%) Proportion (%) 30 50 40 10 60 20 0 20 40 0 60 39 47 AIDS AIDS 11 15 Cancer Cancer 9 12 HCV HCV 7 9 Cardiovascular Cardiovascular 6 6 Bacterial infection Suicide 4 4 Suicide Non-AIDS related infection 2 2 Liver disease Accident 2 2 Accident HBV 2 1 Neurological disorder Overdose 1 2 Iatrogenic Overdose 1 2 HBV Bronchopulmonary disease 1 1 Metabolic Renal failure 1 1 Other infection Liver disease 3 0 Unknown Psychiatric illness 0 Antiretroviral treatment 2 Other 2 Unknown Mortality 2000 (n=964) Mortality 2005 1st quarter (n=405) France Lewden C, et al. Int J Epidemiol.2005;34:121–130 Lewden C et al. J Acquir Immune Defic Syndr 2008;48:590-8

  6. DAD Study: Low and stable incidence of MI in HIV-infected patients 5 4 3 Incidence of MI (per 1000 PYFU) 2 1 0 2003 2007 2008 2009 No. MI 126 345 517 580 PYFU 36199 94969 157912 178835 NEJM 2003; NEJM 2007; Lancet 2008; CROI 2009

  7. Il sole di Austerlitz ?

  8. Molti fattori di rischio….

  9. HIV+ patients with MI have higher prevalence of traditional CV risk factors DAD Study, CROI 2009 (abstract 44LB); French Hospital Database on HIV, CROI 2009 (abstract 43LB)

  10. Incidence of Smoking is Increased among HIV+ vs HIV- Patients 70 APROCO cohort (HIV+) MONICA sample (HIV–) p<0.0001 60 p<0.0001 50 p=NS 40 30 Percent patients p<0.01 20 p=NS 10 0 HDL-C <40 mg/dL LDL-C >160 mg/dL Hypertension Smoking Glucose 126 mg/dL No difference in TC • N=223 HIV+ men and women on PI vs 527 HIV– male • HIV+ have lower HDL and higher TG • Predicted risk of CHD > in HIV+ men (RR=1.2) and women (RR=1.6), p<0.0001 Savès M et al. Clin Infect Dis 2003.

  11. Chronic hepatitis C increases the risk of myocardial infarction in HIV+ patients VA patients *Adjusted for HTN, Age, DM and Tobacco Use Bedimo R et al. World AIDS Conference, Mexico 2008

  12. Peripheral Endothelial Function Decreases after Initiation of cART Kristoffersen US et al. 49th ICAAC. Abs H-1579.

  13. Meanintima-mediathickness Hsue et al AIDS 2009, 23: 1059-67

  14. Trafalgar: l’inizio della mischia

  15. Recent data from DAD shows  risk of MI with cumulative exposure to IDV and LPV/r PI NNRTI 1.2 1.13 RR/year (95%CI) 1 0.9 IDV NFV LPV/r SAQ NVP EFV #PYFU: 68,469 56,529 37,136 44,657 61,855 58,946 #MI: 298 197 150 221 228 221 Incidence 4.4 3.5 4.0 4.9 3.7 4.7 (per 1000 PY) Lundgren JD et al., CROI 2009. Abst 44LB

  16. Incidence 3.8 4.4 5.0 4.2 3.6 4.1 3.5 (per 1000 PYFU) DAD CROI 2009

  17. Quebec Cohort: AMI Risk by NRTI ABC 6 mo ABC any exp ddI 6 mo ddI any exp FTC 6 mo FTC any exp 3TC 6 mo 3TC any exp d4T 6 mo d4T any exp TDF 6 mo TDF any exp ddC 6 mo ddC any exp ZDV 6 mo ZDV any exp Adjusted* hazard ratio of AMI according to exposure to each NRTI in the prior 6 months or any exposure Statistically Significant 1.13 (0.16;8.10) 10 5 0 1.13 (0.16;8.10) 1.95 (0.48;7.93) 2.11 (1.07;4.19) 1.68 (1.14;2.49) 1.68 (0.96;2.94) 1.18 (0.60;2.34) 1.51 (0.98;2.32) 1.47 (0.88;2.45) 1.55 (1.03;2.32) 1.31 (0.90;1.89) 1.48 (1.03;2.13) 1.07 (0.52;2.19) Hazard Ratio (95% CI) 1.69 (1.17;2.44) 1.48 (1.03;2.12) 0.84 (0.58;1.22) * Adjusted for use of anti-diabetic drugs, anti-hypertensive drugs, lipid-lowering drugs, and ant-platelet drugs or warfarin Durand M, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. TUPEB175.

  18. Quebec Cohort: AMI Risk by PI ATV 6 mo ATV any exp IDV 6 mo IDV any exp LPV 6 mo LPV any exp NFV 6 mo NFV any exp RTV 6 mo RTV any exp SQV 6 mo SQV any exp FPV 6 mo FPV any exp Adjusted* hazard ratio of AMI according to exposure to each PI in the prior 6 months or any exposure Statistically Significant 5 0 1.22 (0.57;2.63) 1.68 (1.15;2.44) 1.78 (1.25;2.64) 1.48 (0.55;4.01) 1.32 (0.42;4.16) 1.59 (1.10;2.29) 1.15 (0.58;2.28) 1.01(0.47;2.18) 1.61 (1.07;2.41) 1.38 (0.86;2.22) Hazard Ratio (95% CI) 1.27 (0.89;1.82) 1.06 (0.69;1.62) 1.00 (0.67;1.49) 0.84 (0.47;1.49) * Adjusted for use of anti-diabetic drugs, anti-hypertensive drugs, lipid-lowering drugs, and anti-platelet drugs or warfarin Durand M, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. TUPEB175.

  19. VA Case Registry:Cumulative Abacavir Use and Risk of Myocardial Infarction and Stroke Myocardial Infarction Cerebrovascular Event 1.5 1.8 1.4 1.6 1.3 1.4 1.2 Hazard ratio Hazard ratio 1.1 1.2 1.0 1.0 0.9 0.8 0.8 HAART with ABC HAART with other NRTIs Non HAART therapy HAART with ABC HAART withother NRTIs Non HAARTtherapy Unadjusted HR of AMI for each PY of exposure to each one of the categories Adjusted for most recent estimated GFR (by MDRD method; carried forward). Adjusted for traditional risk factors: age, hyperlipidemia, HTN, type 2 DM, and tobacco use. Bedimo R, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. MOAB202.

  20. VA Case Registry: use of ABC or TDF in Last Regimen and risk of AMI 2.2 2.0 1.8 1.6 1.4 Hazard ratio 1.2 1.0 0.8 0.6 0.4 0.2 NRTI n last regimen during obs. period ABC TFV Both ABC and TFV Unadjusted HR of AMI for each PY of exposure to each one of the categories Adjusted for estimated GFR prior to regimen onset (by MDRD method). Bedimo R, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. MOAB202.

  21. Summary of studies on the association between exposure to abacavir the risk of myocardial infarction

  22. Out of the 418 cases identified, 129 were excluded 45 had incomplete medical records 36 MIs occurred before the study period 2 cases of MI were undated 4 cases of MI occurred before the diagnosis of HIV infection 6 cases had a MI before being enrolled in the cohort 36 cases did not have a confirmed MI Limitations in the definition of event in the French Cohort: Not all “MIs” are “valid MIs” Costagliola D et al. CROI 2009, Abst. 43LB

  23. Impact ofTraditional CV RiskFactors and HIV Parameters on the RiskofMI in HIV Patients Lang S et al. EACS 2009.

  24. Risk factors of MI in HIV infected patients apart from treatment

  25. L’indipendenza ha un prezzo La battaglia di Solferino

  26. Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries. Consecutive patients (men and women </=70 years) were identified after coronary artery bypass graft or percutaneous coronary intervention, or a hospital admission with acute myocardial infarction or ischaemia, and were interviewed at least 6 months later. Koseva et al Lancet 2009, 373: 929-39

  27. Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries Koseva et al Lancet 2009, 373: 929-39 These time trends show a compelling need for more effective lifestyle management of patients with coronary heart disease. Despite a substantial increase in antihypertensive and lipid-lowering drugs, blood pressure management remained unchanged, and almost half of all patients remain above the recommended lipid targets. To salvage the acutely ischaemic myocardium without addressing the underlying causes of the disease is futile; we need to invest in prevention

  28. Una Waterloo….ma c’è anche il punto di vista di Wellington Grazie per l’attenzione

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