1. Long Term Management of HIV Infection in Aging Adults: Current Challenges, Future Strategies Andrew Zolopa, MD Stanford University

2. Aging of HIV Population: San Francisco Population-based HIV registry from 2006-2010 Registry increased from 9,001 to 9,673 mostly due to decline in deaths Those older than 50 now 53% of population, up from 41% in 2006 --fastest growing subset of patients Adapted from Scheer S, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE131. Age Trends of Persons Living with HIV/AIDS in San Francisco

3. Late HAART Era Patients Still Have a 10y Shorter Life Expectancy than HIV- Controls Adapted from Lohse N, et al. Ann Intern Med 2007;146:87–95 Probability of Survival Pre-HAART (1995–1996) Early HAART (1997–1999) Survival from Age 25 Years N= 3,990 1 0.75 0.5 0.25 0 25303540455055606570 Age, years Late HAART (2000–2005) Population controls (See Also: ART-CC, Lancet, 2008; Lewden, JAIDS, 2007)

4. Changing Patterns of the Causes of Death in a Swiss Cohort (SHCS) SHCS is a prospective observational cohort Characteristics of participants that died from 2005-2009 459 deaths/9,053 participants (5.1%) Adapted from Ruppik M, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 789. Causes of Death in Participants in 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

5. Accelerated or Premature Aging in HIV? Increased Frailty CVD Increased Cancer Neurocognitive Impairment Osteoporosis End Organ Dz Potential Causes –Drug Toxicities –Residual HIV –Co-infections –Inflammation

6. Many morbidities associated with aging also appear to be increased in treated HIV disease Bone fractures / osteoporosis [5,6] Cardiovascular disease [1-3] Cancer (non-AIDS) [4] Liver disease [7] Renal disease [8] Cognitive decline [9] Frailty [10] Non-AIDS infections [11] 1. Klein D, et al. J Acquir Immune Defic Syndr. 2002;30:471-477. 2; Hsue P, et al. Circulation. 2004;109:316-319. 3. Grinspoon SK, et al. Circulation. 2008;118:198-210. 4. Patel P, et al. Ann Int Med, 2008;148:728-736. 5. Triant V, et al. J Clin Endocrinol Metab. 2008;93:3499-3504. 6. Arnsten JH, et al. AIDS. 2007 ;21:617-623. 7. Odden MC, et al. Arch Intern Med. 2007;167:2213-2219. 8. Choi A, et al. AIDS, 2009;23(16):2143-49. 9. McCutchan JA, et a. AIDS. 2007 ;21:1109-1117. 10. Desquilbet L, et al. J Gerontol A Biol Sci Med Sci. 2007;62:1279-1286; Sogaard OS, et al., Clin Infect Dis, 2008; 47:1345-53.

7. Non-AIDS morbidities are more common in HIV, even after adjustment for age, HAART exposure and traditional risk factors Lifestyle HAART Toxicity HAART Toxicity Persistent Inflammation Persistent Inflammation Premature Aging Premature Aging Adapted from Deeks and Phillips, BMJ, 2009

8. SMART: Untreated HIV Disease Associated With Increased Risk of Non-AIDS Morbidity Adapted from El Sadr W, et al. N Engl J Med. 2006;355:2283-2296.

9. SMART: Inflammatory Markers Strongly Associated With Mortality and CVD Events Adapted from Kuller LH, et al. PLoS Med. 2008 ;5: e203. doi:10.1371/journal.pmed.0050203.

10. Microbial Translocation Due to a “Leaky” Gut Cohen J. Science. 2008 319:888

11. Early Immune Senescence: A Model for Premature Aging in HIV Desai S, Landay A. Curr HIV AIDS Rep 2010;7: 4-10.

12. Prevalence of Lipodystrophy in Current ART Era Cross-sectional study of HIV patients at Australian clinic, comparing 1998 to 2010 −Definition of lipodystrophy (LD) from original case definition Results: −Participants older, healthier from HIV and CV risk factor perspective −Prevalence of study-defined LD has declined from 69 to 58% −In multivariate analysis, use of tenofovir or abacavir associated with significantly lower risk Conclusion: Although prevalence of LD has declined, it remains relatively common – especially in long-term survivors Adapted from Price J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOPE264. Characteristic1998 (n=144)*2010 (n=100)*p-value Age (years)42.1 ± 0.7451.8 ± 0.87<0.0001 Smoking: n (%)73 (51)36 (36)<0.0001 HIV Duration (mos.)86.2 ± 4.6165.0 ± 10.4<0.0001 ART Duration (mos.)36 (21-72)129 (51-169)<0.0001 CD4 Count (cells/mm 3 )320 (178-560)585 (403-754)<0.0001 HIV VL (copies/mL)250 (250-9800)250 (250-250)<0.0001 Undetectable VL: n (%)78 (57)90 (90)<0.0001 Prevalence of LD: %69580.02

13. Adapted from PROGRESS 96 Week Results April 9, 2011 PROGRESS study Week 96 (TLOVR)

14. Adapted from PROGRESS Bone Mineral Density July 14, 2011 Mean Percent Changes in Bone Mineral Density Analyzed Using DXA through 96 Weeks of Treatment

15. Strategies For Long-term ART Preferred ART regimens currently focus on: –effectiveness of viral suppression –relatively short-term safety Are preferred ART regimens the same for long- term treatment (i.e. decades)? Long-term ART goal: reducing toxicity –Fewer drugs –Use ART with “high genetic barrier to resistance” –Compartment penetration?

16. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir Adapted from ACTG A5262 Team. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS. 2011 Nov 13;25(17):2113-22.