Post on 18-Nov-2014
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Long Term Management of HIV Infec2on in Aging Adults:
Current Challenges, Future Strategies
Andrew Zolopa, MD Stanford University
Aging of HIV Popula2on: San Francisco
• Popula:on-‐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 popula:on, up from 41% in 2006 -‐-‐fastest
growing subset of pa:ents
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
Late HAART Era Pa2ents S2ll Have a 10y Shorter Life Expectancy than HIV-‐ Controls
Adapted from Lohse N, et al. Ann Intern Med 2007;146:87–95
Prob
ability of S
urvival
Pre-‐HAART (1995–1996)
Early HAART (1997–1999)
Survival from Age 25 Years N= 3,990
1
0.75
0.5
0.25
0
25 30 35 40 45 50 55 60 65 70
Age, years
Late HAART (2000–2005)
Popula2on controls
(See Also: ART-‐CC, Lancet, 2008; Lewden, JAIDS, 2007)
Changing PaXerns of the Causes of Death in a Swiss Cohort (SHCS)
• SHCS is a prospec2ve observa2onal cohort • Characteris2cs of par2cipants that died from 2005-‐2009 • 459 deaths/9,053 par2cipants (5.1%)
Adapted from Ruppik M, et al. 18th CROI; Boston, MA; February 27-‐March 2, 2011. Abst. 789.
Causes of Death in Par2cipants in the Swiss HIV Cohort Study in 3 Different Time Periods, and in the Swiss Popula2on in 2007
Years of Death of HIV+ Persons Versus Swiss Popula2on
Accelerated or Premature Aging in HIV?
• Increased Frailty • CVD Increased • Cancer • Neurocogni2ve
Impairment • Osteoporosis • End Organ Dz • Poten2al Causes
– Drug Toxici2es – Residual HIV – Co-‐infec2ons – Inflamma2on
Many morbidi2es 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]
• Cogni2ve decline [9]
• Frailty [10] • Non-‐AIDS infec2ons [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.
Non-‐AIDS morbidi2es are more common in HIV, even ager adjustment for age, HAART
exposure and tradi2onal risk factors
Lifestyle
HAART Toxicity
Persistent Inflamma2on
Premature Aging
Adapted from Deeks and Phillips, BMJ, 2009
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.
SMART: Inflammatory Markers Strongly Associated With Mortality and CVD Events
Biomarker
All-‐Cause Mortality (N=85)
Fatal or Non-‐fatal CVD (N=136)
OR P-‐value OR P-‐value
hs-‐CRP 3.5 0.004 1.6 0.20
IL-‐6 12.6 <0.0001 2.8 0.003
Amyloid A 2.3 0.08 1.6 0.12
Amyloid P 1.1 0.90 2.8 0.002
D-‐dimer 13.3 <0.0001 2.0 0.06
F1.2 1.4 0.45 0.8 0.56
Adapted from Kuller LH, et al. PLoS Med. 2008 ;5: e203. doi:10.1371/journal.pmed.0050203.
Microbial Transloca2on Due to a “Leaky” Gut
Cohen J. Science. 2008 319:888
Early Immune Senescence: A Model for Premature Aging in HIV
Desai S, Landay A. Curr HIV AIDS Rep 2010;7: 4-‐10.
Prevalence of Lipodystrophy in Current ART Era
• Cross-‐sec:onal study of HIV pa:ents at Australian clinic, comparing 1998 to 2010 − Defini:on of lipodystrophy (LD) from original case defini:on
• Results: − Par:cipants older, healthier from HIV and CV risk factor perspec:ve − Prevalence of study-‐defined LD has declined from 69 to 58% − In mul:variate analysis, use of tenofovir or abacavir associated with
significantly lower risk • Conclusion: Although prevalence of LD has declined, it remains rela:vely common
– especially in long-‐term survivors
Adapted from Price J, et al. 6th IAS; Rome, Italy; July 17-‐20, 2011. Abst. MOPE264.
Characteris2c 1998 (n=144)* 2010 (n=100)* p-‐value
Age (years) 42.1 ± 0.74 51.8 ± 0.87 <0.0001
Smoking: n (%) 73 (51) 36 (36) <0.0001
HIV Dura2on (mos.) 86.2 ± 4.6 165.0 ± 10.4 <0.0001
ART Dura2on (mos.) 36 (21-‐72) 129 (51-‐169) <0.0001
CD4 Count (cells/mm3) 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: % 69 58 0.02
Adapted from PROGRESS 96 Week Results April 9, 2011
PROGRESS study Week 96 (TLOVR)
Adapted from PROGRESS Bone Mineral Density July 14, 2011
Mean Percent Changes in Bone Mineral Density Analyzed Using DXA through 96 Weeks of Treatment
Strategies For Long-‐term ART
• Preferred ART regimens currently focus on: – effec:veness of viral suppression – rela:vely 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 gene:c barrier to resistance” – Compartment penetra:on?
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 pa:ents (ACTG A5262). AIDS. 2011 Nov 13;25(17):2113-‐22.