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Cardiovascular risk in naïve patients

Cardiovascular risk in naïve patients. HIV Symposium – Latin America & Caribbean Miami, March 2013. Dr. Carlos Beltrán Grupo SidaChile Hosp Barros Luco Trudeau Universidad de Santiago. CV risk factors in HIV (-) & HIV (+). 21,0% / 6,0%: < 40 años.

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Cardiovascular risk in naïve patients

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  1. Cardiovascular risk in naïve patients HIV Symposium – Latin America & Caribbean Miami, March 2013 Dr. Carlos Beltrán Grupo SidaChile Hosp Barros Luco Trudeau Universidad de Santiago

  2. CV risk factors in HIV (-) & HIV (+) 21,0% / 6,0%: < 40 años 34,0% / 14,4%: > 50 años Guaraldi G, et al. Clin Infect Dis. 2011; 53: 1120-1126

  3. Impact of VL in traditional CV risk factors *Ajustado por edad, sexo, raza, hipertensión, diabetes, dislipidemia * * * Squillace N, et al. J AIDS 2009; 52: 459 - 464

  4. Risk of AMI in HIV + and HIV - patients HIV positive Observed Predicted HIV negative 7 6 5 Incidence of AMI per 1000 PY 4 3 2 1 Duration of ART (y) 0 0 <1 1-2 2-3 3-4 4+ Adjusted for age, gender, etnicity, hypertension, diabetes, dyslipidemia According to Framingham in D:A:D Sudy 100 90 77.7 80 70 60 50 Events per 1000 Pt/year 40 33.4 30 24.5 18.7 20 14.8 10.1 7.6 4.7 10 3.3 0.9 0 18 - 34 35 - 44 45 - 54 55 - 64 65 - 74 Age Triant V, et al. Increased AMI rates in HIV. J Clin Endocrinol Metab 2007; 92: 2506 – 2512 Law M, et al. HIV Med. 2006; 7: 218-230

  5. Role of inflammation CV risk according to Framingham, adjusted for CRP Ridker P, et al. N Engl J Med 2002; 347: 1557 Baker, J et al for the INSIGHT SMART. JAIDS 2011; 56: 36 – 43

  6. Atherosclerosis • Macrophage recruitment → Foamy cells • γIFN, TNF, IL6,7,8, CPR production • LDL Cholesterol retention and oxidation • Endothelial activation; misbalance damage - repair

  7. “Human Inflammatory Virus”

  8. Arteries of HIV positive pts older than HIV negative counterparts

  9. HIV HIV HIV HIV CV risk factors and HIV Genetics Tobacco Gender Life styles Age Abdominal obesity CV Risk Hyper-tension Lipids - Diabetes Insulin resistance Metabolic syndrome

  10. Cardiovascular risk in HIV + patients

  11. PI* NNRTI ATV no RTV (PYFU: 9611) Any ATV(PYFU: 37,005) ATV with RTV (PYFU: 31,232) 1.2 0.8 MI incidence/1000 PYFU (95% CI) 1.13 0.6 RR/año (95% CI) 0.4 1 0.2 0.9 0.0 >3 > 3 > 3 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 None None None > 0, < 1 > 0, < 1 > 0, < 1 > 1, < 2 > 2, < 3 > 2, < 3 > 1, < 2 > 2, < 3 > 1, < 2 Yrs of Exposure D:A:D: PI/ NNRTI y risk of AMI Cumulative Exposure & AMI (adjusted for metabolic changes) Lundgren JD, et al. 16th CROI; Montreal, Canada; February 8-11, 2009. Abst. 44LB D’Arminio Monforte A, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 823

  12. HAART and Metabolic syndrome Wand H et al. AIDS 2007; 21: 2445 - 53 Mallon P et al. AIDS 2003; 17: 971

  13. Activation persists on HAART Hunt P et al. J Infect Dis 2008; 197: 126 - 133

  14. A 49-year-old MSM with recently diagnosed HIV infection presented to care in A2 stage BMI normal, no hypertension. Glucose and Total cholesterol normal Tobacco use +, Triglycerides 850 mg/ dL (UNL 150) Case study

  15. What to do? • Start HAART immediately for his high CV risk • Modify lifestyle (tobacco & diet) and check lipids, CD4 and VL in 3 months without considering HAART initiation for its negative metabolic impact • Explore willingness to HAART initiation, modifying lifestyle and checking lipids in the meantime Please vote

  16. 100 VIH+ VIH- P = .033 80 P = .014 64 60 58 60 Pts con niveles deseados de lípidos a 6 meses (%) 43 40 28 25 20 11 11 0 CT TG LDL HDL Lifestyle and lipid lowering drugs Townsend ML, et al. Int J STD AIDS. 2007;18:851-855 Hollowell S, et al. ICAAC 2005. Abstract H-338 Fitch K et al. AIDS 2006; 20: 1843 - 1850

  17. Still smoking, started on diet and exercises with nice reduction in triglycerides levels He shows some concerns about body shape changes with HAART Severe CD4 count decrease Case study

  18. What to start with? (2013) • TDF/FTC/Efavirenz • TDF/FTC/Atazanavir/r • TDF/FTC/Raltegravir • Abacavir/3TC/Atazanavir Please vote

  19. Impact of 3rd drug in lipids (W96) STARTMRK CASTLE ARTEMIS Raltegravir (n=281) Efavirenz (n=282) Atazanavir + RTV (n=441) Lopinavir/r (n=437) Darunavir + RTV (n=343) Lopinavir/r (n=348) +66* Change (mg/dL) Change (mg/dL) Change (mg/dL) +40* +38* +36‡ +36‡ +35* +26 +21* +20 +17 +18 +17 +15 +14 +13 +10* +10 +10 +8† +7 +7 +5 +3 -4 TC TG LDL-C HDL-C TC TG TC TG LDL-C HDL-C LDL-C HDL-C Lennox J, et al. Lancet 2009; 374: 796 - 806 Molina J, et al. JAIDS 2010; 53: 323 – 331 Mills A, et al. AIDS 2009; 23: 1679 - 1688

  20. Metabolic impact of low RTV dose in HIV (-) volunteers RTV 100 mg BID x 14 d ► 7 d Washout ► LPV/r x 14 d *P ≤0.01 change from baseline Shafran SD et al. HIV Med. 2005;6:421-425

  21. Follow up AZT+3TC+EFV Dec 2004 HAART changed to AZT+3TC+ATV 400 HAART switch to ABC+3TC+ATV 400 Switch to ??? Gemfibrozil Metformin • Aug 2011 thoracic pain & syncope • Nov 2011 ST changes in stress test

  22. What to switch to? (2013) • TDF/FTC/Atazanavir 400 mgs • TDF/FTC/Atazanavir/r • TDF/FTC/Raltegravir • Abacavir/3TC/Rategravir • TDF/FTC or Abacavir/3TC + Maraviroc Please vote

  23. Switch to Ral from LPV/r or any PI (SWITCHMRK 1 & 2 - SPIRAL) 20 RAL + ARTs LPV/r + ARTs 10 0 1% 2% 4% 2% 1% 8% -1% -2% -10 P=0.704 nps** Change from baseline at week 12, mean% -13% -15% P<0.001 -20 P<0.001 -30 -40 -41% -43% P<0.001 P<0.001 -50 Fasting Non Fasting Fasting Fasting Fasting Cholesterol HDL-C Triglycerides* LDL-C HDL-C Triglycerides* Eron J, et al. 16th CROI; Montreal, Canada; 2009. Abst. 70aLB Martinez E, et al. 19th CROI 2012. Abst. 834

  24. Vitamina D Lavie C et al. J Am Coll Cardiol 2011; 58: 1547 - 1556. Brondum – Jacobsen. Metanálisis. Arterioscler Thromb Vasc Biol 2012 Aug 30; epub

  25. Prasugrel Ticagrelor

  26. 2013 Chilean guidelines HAART initiation below 350 CD4+ HAART at any CD4 count in: Older than 50 years old More than one additional CV risk factor Diabetes or Chronic Kidney Disease What to use in this patients? Avoid PIs except ATV Raltegravir when metabolic abnormalities persist

  27. XVI CONGRESO PANAMERICANO DE INFECTOLOGÍA Santiago de Chile / 28 Mayo al 1 Junio de 2013

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