2. Cardiovascular Complications of HIV Mark Boyd MD, FRACP The Kirby Institute for infection and immunity in society 7 th IAS Conference Kuala Lumpur, Malaysia 03 July 2013

3. Cardiovascular Complications of HIV Conflicts of interest GrantsHonorariaAbbVie Gilead SciencesBoehringer-Ingelheim MerckBristol Myers Squibb Janssen-Cilag Merck

4. Cardiovascular Complications of HIV Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

5. Cardiovascular Complications of HIV Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

6. Myocardial Infarction rates in HIV+ versus HIV- Triant J, et al. Clin Endocrinol Metab. 2007. Mean MI rate = 11 v 7 per 1000 person years RR=1.7

7. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

8. Risk factors CVD HIV+ vs HIV- Kaplan R, et al. CID 2007. Dyslipidaemia Smoking Insulin resistance HIV-neg men HIV-pos men HIV-neg women HIV-pos. women

9. Comorbidity distribution * Schouten J et al. World AIDS Conference July 2012; updated May 2013 (personal communication, Reiss P)

10. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

11. SMART - major CVD, hepatic or renal disease No. of patients with events Endpoints Major CVD, hepatic or renal disease 104 CVD, fatal or non-fatal79 Favours VS ► ► Favours DC Relative risk (95% CI) Renal disease, fatal or non-fatal11 1.6 Hepatic disease, fatal or non-fatal17 4.5 1.4 1.7 El-Sadr W, et al. SMART. NEJM 2006

12. Cardiovascular complications of HIV SMART: risk of death strongly associated with IL-6 & D-dimer biomarker levels at study entry Biomarker<25 th percentile (reference) 25 th -49 th percentile 50th-74 th percentile >75 th percentile p-value OR (95%CI) OR (95 t% CI) OR (95 % CI) IL-6 (inflammation) 1.01.5 (0.7-3.1) 3.2 (1.3-7.9) 8.3 (3.3-20.8) <0.0001 D-dimer (coagulation) 1.03.2 (1.1-9.0) 4.0 (1.3-12.3) 12.4 (4.3-37.0) <0.0001 Kuller L, et al. PLoS Med 2008

13. Untreated HIV infection and CVD pathogenesis: a proposed model Baker J and Lundgren J. Eur Heart J 2011

14. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

15. Cardiovascular complications of HIV ART and myocardial infarction Friis-Moller N, et al. D:A:D. NEJM 2003. MI incidence according to duration of ART exposure

16. MI risk disease by ARV exposure in D:A:D Worm S, et al. D:A:D. JID 2012. ART exposure and MI risk in D:A:D Cardiovascular complications of HIV

17. Untreated HIV infection and CVD pathogenesis: a proposed model Baker J and Lundgren J. Eur Heart J 2011

18. Treated HIV infection and CVD pathogenesis: a proposed model Baker J and Lundgren Eur Heart J. 2011 ART Insulin resistance

19. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

20. Myocardial Infarction Never smoked 5 - 1 - Previous Baseline status < 1 yr1-2 yrs2-3 yrs3+ yrsCurrent Stopped smoking during follow-up Adjusted for: age, sex, cohort, calendar year, antiretroviral treatment, family history of CVD, diabetes, and time-updated lipids and blood pressure assessments 0.5 - D:A:D study group. HIV Med 2011. Stop Smoking

21. Cardiovascular disease in HIV Prevention: monitor and modify risks Petoumenos K for D:A:D. 20 th CROI 2013. Reduce TC 1 mmol/L Stop smoking CVD hazard in D:A:D* Reduce sysBP 10 mmHg *relative to 40 y.o. HIV+ male

22. Control dyslipidaemia: use TDF TDF (n=170) d4T (n=162) p-value Total-cholesterol (mmol/L) +0.78+1.50<0.001 HDL-cholesterol (mmol/L) +0.23+0.16 0.003 LCL-cholesterol (mmol/L) +0.36+0.67<0.001 TG (mmol/L) +0.01+1.51<0.001 Total limb fat gain-DXA (kg) +8.6+4.5<0.001 Total weight gain (kg) +2.9+0.6 0.001 Neuropathy3%10%<0.001 Gallant J, et al. GS 934 study. JAMA 2004;292:191-201.

23. CVD complications of HIV Ahmed H et al. MESA. Am J Epi 2013. Prevention: adopt a healthy lifestyle Probability of CHD according to health score Score 0 Score 2 Score 3 & 4

24. CVD complications of HIV Ahmed A, et al. MESA. Am J Epi 2013. Prevention: adopt a healthy lifestyle Probability of death according to health score Score 3 & 4 Score 2 Score 1 Score 0

25. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

26. CVD complications of HIV: key messages Walker S, et al. DART. Lancet 2009. ART saves lives

27. CVD complications of HIV: key messages 3 year riskOff ARTOn ART AIDS/Death23 - 29%6 - 11% AMI0.3% (0.2-0.38) 1% (0.43-1.77) Law M et al. HIV Med 2003. The risk of death from AMI is much less than the risk of dying from untreated HIV-infection

28. CVD complications of HIV: key messages Monitor and treat modifiable risk factors Stop smoking Monitor& treat hypertension Monitor & treat dyslipidaemia and diabetes Encourage healthy weight, diet and exercise Monitor and treat HIV-infection –according to guidelines –there is no evidence to support use of specific ART regimens for PLHIV with high-risk for CVD

29. Cardiovascular Complications Outline Epidemiology Risk factors –host –virus-host –ART Prevention Key messages Conclusions

30. Cardiovascular Complications of HIV Conclusions Cardiovascular disease pathogenesis in HIV is complex While HIV factors may add to complexity, conventional risk factors are prominent Risks can be monitored and modified Primary prevention is key in low-, middle- and high-income settings