1. NCD Complications in HIV Patients Esteban Martinez Hospital Clínic University of Barcelona Barcelona SPAIN esteban@fundsoriano.es Washington D.C., USA, 22-27 July 2012www.aids2012.org

2. 0 10 20 30 40 50 60 70 80 84868890929496980002 0 500 1000 1500 2000 2500 3000 ACTIVE PATIENTS New patients Deaths Data from Hospital Clinic, Barcelona This means long-term exposure to ART and higher risk for non-HIV-related conditions Mortality per 100 patient-years Number of patients HIV infection has changed from a fatal disease into a chronic condition www.aids2012.org

3. Martinez et al. HIV Medicine 2007; 8: 251-258 Mortality per 100 person-years Significant reduction in mortality for HIV-infected patients over this period (P<0.001; χ 2 test for trend), but not for the general population (P<0.936; χ 2 test for trend) Annual incidence of mortality in the Hospital Clínic HIV-infected cohort compared with general population aged 16-65 years in Catalonia HIV-infected cohort General population Mortality in HIV-infected adults is still higher than that in general population www.aids2012.org

4. Ruppik M, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 789. Causes of death in participants from the Swiss HIV Cohort Study in 3 different time periods, and in the Swiss Population in 2007 Years of Death of HIV+ Persons Versus Swiss Population AIDS-related deaths have decreased, but non-AIDS-related ones have increased

5. Non-AIDS-related NCDs in HIV+patients are higher with older age Hasse B et al. Clin Infect Dis 2011; 53: 1130-1139 Swiss HIV Cohort Study www.aids2012.org

6. The following co-morbidities were analysed: Hypertension, Type 2 Diabetes, Cardiovascular Disease and Osteoporosis. Co-morbidities prevalence was higher in cases than controls in all age strata (all p-values <0.001). Comorbidities not only more common with increasing age but also occur earlier in HIV Co-mobidities prevalence in cases and controls, stratified by age categories. Guaraldi G et al. Clin Infect Dis 2011; 53: 1120-1126 www.aids2012.org

7. A RR 1.75 p <0.0001* 0 2 4 6 8 10 12 HIV+HIV- Events Per 1000 PYs B 0 20 40 60 80 100 18-3435-4445-5455-6465-74 Age Group (Years) Triant V et al. J Clin Endocrinol Metab 2007; 92: 2506-2512 * Adjusted for age, gender, race, hypertension, diabetes and dyslipidaemia. Proportion of patients with hypertension, diabetes and dyslipidaemia significantly higher in HIV-positive vs HIV-negative cohort n = 1,044,589 n = 3,851 # of MI 189 26,142 Events Per 1000 PYs HIV-infected patients have a higher incidence of myocardial infarction

8. Brown TT & Qaqish RB. AIDS 2006; 20: 2165-2174 HIV+ patients have a higher prevalence of low bone mineral density www.aids2012.org

9. 0 0.5 1 1.5 2 2.5 3 3.5 AllVertebralHipWrist Fracture prevalence/100 persons Triant VA et al. J Clin Endocrinol Metab 2008; 93: 3499–3504 Population-based study 8,525 HIV-infected patients 2,208,792 non HIV-infected patients HIV+ HIV- p<0.0001 P<0.0001 p<0.0001 p=0.001 Greater rate of fractures in HIV- infected patients vs un infected individuals

10. Liver DiseaseRenal Disease Goulet J. Clin Infect Dis 2007; 45: 1593-1601 Liver and kidney comorbidities more common in HIV+ patients www.aids2012.org

11. Heaton R et al. J Neurovirol 2011; 17: 3-16 Percent impaired Neurocognitive impairment remains highly prevalent despite of cART Pre-cART cART HIV+

12. Patel P et al. Ann Intern Med 2008; 148: 728-736 Cancer Type, Observed Rate per 100,000 Person-Years (95% CI) ASD/HOPS (157,819 Person-Years) SEER (334,802,121 Person-Years) SRR* (95% CI) Anal51.4 (40.8-63.9)1.5 (1.4-1.5)42.9 (34.1-53.3) Vaginal33.9 (18.0-57.9)3.2 (3.2-3.3)21.0 (11.2-35.9) Hodgkin’s lymphoma51.4 (40.9-63.9)3.3 (3.3-3.4)14.7 (11.6-18.2) Liver31.7 (23.5-41.8)5.3 (5.2-5.4)7.7 (5.7-10.1) Lung88.8 (74.7-104.8)67.5 (67.2-67.7)3.3 (2.8-3.9) Melanoma24.7 (17.6-33.8)18.4 (18.3-18.6)2.6 (1.9-3.6) Oropharyngeal33.0 (24.6-43.3)16.1 (16.0-16.2)2.6 (1.9-3.4) Leukemia15.2 (9.8-22.7)12.2 (12.1-12.3)2.5 (1.6-3.8) Colorectal47.0 (36.9-59.0)52.0 (51.7-52.2)2.3 (1.8-2.9) Renal14.0 (8.8-21.1)13.0 (12.8-13.1)1.8 (1.1-2.7) Prostate32.7 (23.3-44.7)173.5 (172.9-174.1)0.6 (0.4-08) ASD, Adult and Adolescent Spectrum of Disease Project; HOPS, HIV Outpatient Study; SEER, Surveillance, Epidemiology, and End Results, 1992–2003; *SRR, standardized rate ratio calculated as ASD/HOPS to SEER populations. Non-AIDS–defining cancer rates higher in HIV+ patients vs general population www.aids2012.org

13. http://www.europeanaidsclinicalsociety.org/guidelinespdf/2_Non_Infectious_Co_Morbidities_in_HIV.pdf

14. EACS guidelines http://www.europeanaidsclinicalsociety.org/guidelinespdf/2_Non_Infectious_Co_Morbidities_in_HIV.pdf

15. http://www.aahivm.org/hivandagingforum www.aids2012.org

16. Growing interest in learning about pathogenesis and care of comorbidities

17. http://hp2010.nhlbihin.net/atpIII/calculator.asp?usertype=prof Most basic screening tools for NCDs are easily affordable

18. Others may be not so easily affordable: DXA needed for measuring BMD www.aids2012.orgWashington D.C., USA, 22-27 July 2012

19. http://www.europeanaidsclinicalsociety.org/guidelinespdf/2_Non_Infectious_Co_Morbidities_in_HIV.pdf

21. % participants ComedicationsComorbidities N= 5761 2233 450 5761 2233 450 Hasse B et al. Clin Infect Dis 2011; 53: 1130-1139 The need of polypharmacy means higher risk for interactions and toxicities Swiss HIV Cohort Study www.aids2012.org

22. Summary The HIV infected population is ageing and NCDs are becoming more prevalent as a cause of morbidity and mortality There is an increasing awareness for screening and management of NCDs in HIV+ patients and specific cost- effective guidelines have been issued Prevention and management for NCDs should be routinely included into the clinical care of HIV+ patients Issues of NCDs screening and management cost, overlapping toxicity of antiretrovirals, and risk of drug interactions will need to be continuously addressed www.aids2012.orgWashington D.C., USA, 22-27 July 2012

23. Special thanks: To my colleagues from the HIV Unit at Hospital Clínic, Barcelona, and particularly to Jose Gatell Also to Pere Domingo, Omar Sued, Giovanni Guaraldi, and Julian Falutz for their valuable input To Jordi Blanch, co-organiser of the annual HIV & Neuropsychiatry Symposium in Barcelona and to all the contributors to the recent 2011 version of European AIDS Clinical Society (EACS) guidelines www.aids2012.orgWashington D.C., USA, 22-27 July 2012