BHIVA AUTUMN CONFERENCE 2012 Including CHIVA Parallel Sessions Dr Duncan Churchill Royal Sussex County Hospital, Brighton COMPETING INTEREST OF FINANCIAL VALUE > 1,000: Speaker Name Statement Duncan Churchill None Date 22 September 2012 4-5 October 2012, Queen Elizabeth II Conference Centre, London
Cardiovascular disease and antiretrovirals Duncan Churchill Brighton and Sussex University Hospitals NHS Trust
Should we start ARVs earlier in people with high CVD risk? How should we measure CVD risk? Should we modify ARVs in people with high CVD risk?
New HIV and AIDS diagnoses and deaths People living with diagnosed HIV infection New HIV and AIDS diagnoses, people living with diagnosed HIV, and deaths: United Kingdom, 2001-2010 9000 8000 Numbers with diagnosed HIV infection HIV diagnoses AIDS diagnoses Deaths 80000 70000 7000 6000 5000 4000 3000 2000 60000 50000 40000 30000 20000 1000 10000 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 0 HIV and AIDS Reporting System HIV and STI Department, Health Protection Agency - Colindale
Persons seen for HIV care HIV diagnosed persons seen for HIV care by age group*: UK, 2002-2011 80,000 70,000 60,000 50,000 40,000 50+ 35-49 25-34 15-24 <15 30,000 20,000 10,000 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 *Excludes persons with age not reported, 15 in 2002 and 0 in 2011. HIV and AIDS Reporting System HIV and STI Department, Health Protection Agency - Colindale
Brighton cohort HIV and ageing 100% 90% 15% 17% 17% 19% 20% 22% 23% 23% 25% 27% 28% 80% 30% 32% 70% 60% 50% 72% 70% 72% 70% 70% 40% 70% 68% 67% 66% 65% 63% 61% 59% 30% 20% 10% 0% 13% 13% 10% 10% 10% 9% 9% 9% 9% 9% 9% 8% 8% 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 % HIV cohort aged <30 % HIV cohort aged 30-50 % HIV cohort aged >50
Bozzette et al., NEJM 2003; 348: 702-710
Increased risk of CVD in HIV Islam et al. HIV Medicine 2012, 13: 453-468
Should people with high CVD risk start antiretrovirals earlier?
% with a Major CVD Event SMART Study Risk of CVD with ART Interruptions 20 15 10 5 DC Death from CVD 7 4 VS Non-fatal clinical MI 12 12 Non-fatal silent MI 11 5 Non-fatal stroke 8 3 Coronary artery disease requiring surgery for invasive procedure 22 14 All major CVD events 48 31 DC No. at Risk DC VS VS 0 0 0.5 1 1.5 2 2.5 3 3.5 4 Years from Randomization 2752 1306 713 379 10 2720 1292 696 377 10 Phillips A, et al. 14th CROI, Los Angeles, CA, February 25-28, 2007. Abst. 41.
Baseline characteristics of deaths + controls in SMART Deaths (n=85) Controls (n=170) P-value Age (median) 50 48 0.007 CD4 (median) 545 614 0.03 Prior AIDS (%) 31.8 26.5 0.36 Current smoker (%) 57.6 31.8 0.0001 Diabetes (%) 25.9 14.7 0.03 Antihypertensive medication (%) 38.8 25.3 0.02 Prior CVD (%) 11.8 4.7 0.04 7/85 deaths due to AIDS Kuller et al. CROI 2008
Should people with high CVD risk start SMART ARVs earlier? Virological suppression associated with reduced CVD events (not significant) HOPS CD4 <350 greater risk of CVD CD4 350-500 no increased risk D:A:D Treated HIV associated with increased risk of MI Longer treatment associated with increased risk
NEJM 2003; 349: 1993-2003
Islam et al. HIV Medicine 2012, 13: 453-468
Should we start ARVs earlier in people with high CVD risk? Probably not How should we measure CVD risk?
Managing cardiovascular risk
Assessment of CVD risk Framingham CHIP Q risk BHIVA monitoring guidelines 2011
cvrisk.mvm.ed.ac.uk/calculator/framingham.htm
http://www.cphiv.dk/tools/dadriskequations/tabid/437/default.aspx
http://www.qrisk.org
41 year old MSM Ex-smoker (stopped 10 cigarettes/day 10 years ago) BP 120/82 Total cholesterol 4.3 HDL cholesterol 1.3
JBS2 - Thresholds for intervention Everyone: Stop smoking Increase aerobic exercise Achieve optimal weight and weight distribution Make healthier food choices Clinical evidence of CVD Diabetes mellitus CVD risk of >20% BP > 160 systolic, or >100 diastolic or target organ damage Cholesterol: HDL >6.0 Familial dyslipidaemia
Incidence rate ratio of MI related to smoking history in the D:A:D study HIV Medicine 2011; 12: 412-421
How would you assess CVD risk? Framingham calculator JBS/BNF calculator CHIP CVD risk assessment tool Qrisk Other Don t know I wouldn t his risk is low Vote
Which calculator? Framingham JBS2 ASSIGN CHIP Qrisk Advantage Different time scales Different end points Corresponds to JBS guidance Tailored to Scottish population Uses family history, deprivation Developed for HIV Incorporates drug history Widely used in general practice Incorporates postcode, rheumatoid, diabetes, renal disease etc. Disadvantage Not validated for other populations
Should we start ARVs earlier in people with high CVD risk? Probably not How should we measure CVD risk? That depends Should we modify ARVs in people with high CVD risk?
Managing cardiovascular risk
RR of cumulative exposure/year 95%CI RR of recent* exposure yes/no 95%CI RR of cumulative exposure/year 95%CI D:A:D: Recent and/or Cumulative Antiretroviral Exposure and Risk of MI 1.9 NRTI 1.9 1.5 1.2 1.0 0.8 1.5 1.2 1.0 0.8 0.6 ZDV ddi ddc d4t 3TC ABC TDF # PYFU: 138,109 74,407 29,676 95,320 152,009 53,300 39,157 # MI: 523 331 148 40 554 221 139 1.2 PI NNRTI 1.13 1.1 0.6 1.0 0.9 IDV NFV LPV/RTV SQV NVP EFV # PYFU: 68,469 56,529 37,136 44,657 61,855 58,946 # MI: 298 197 150 221 228 221 *Current or within last 6 months. Approximate test for heterogeneity: P = 0.02 Lundgren JD, et al. CROI 2009. Abstract 44LB. Graphics reproduced with permission.
Lancet 2008; 371: 1417-1426
41 year old MSM Ex-smoker (stopped 10 cigarettes/day 10 years ago) BP 120/82 Total cholesterol 4.3 HDL cholesterol 1.3 On Kivexa and Kaletra for 9 years
Would you Leave him on Kivexa/Kaletra Switch Kivexa only Switch Kaletra only Switch both drugs