Long Term Management of HIV Infection in Aging Adults: Current Challenges, Future Strategies Andrew...
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Long Term Management of HIV Infection in Aging Adults:
Current Challenges, Future Strategies
Andrew Zolopa, MDStanford University
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
Late HAART Era Patients Still Have a 10yShorter Life Expectancy than HIV- Controls
Adapted from Lohse N, et al. Ann Intern Med 2007;146:87–95
Prob
abili
ty o
f Sur
viva
l
Pre-HAART (1995–1996)
Early HAART (1997–1999)
Survival from Age 25 YearsN= 3,990
1
0.75
0.5
0.25
0
25 30 35 40 45 50 55 60 65 70Age, years
Late HAART (2000–2005)
Population controls
(See Also: ART-CC, Lancet, 2008; Lewden, JAIDS, 2007)
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
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
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.
Non-AIDS morbidities are more common in HIV, even after adjustment for age, HAART
exposure and traditional risk factors
LifestyleLifestyle
HAARTToxicityHAARTToxicity
PersistentInflammation
PersistentInflammation
PrematureAging
PrematureAging
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
Adapted from Kuller LH, et al. PLoS Med. 2008 ;5: e203. doi:10.1371/journal.pmed.0050203.
Microbial Translocation 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-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.
Characteristic 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 Duration (mos.) 86.2 ± 4.6 165.0 ± 10.4 <0.0001
ART Duration (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 ResultsApril 9, 2011
PROGRESS studyWeek 96 (TLOVR)
Adapted from PROGRESS Bone Mineral DensityJuly 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:
– 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?
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 raltegravirin treatment-naive HIV-1-infected patients (ACTG A5262). AIDS. 2011 Nov 13;25(17):2113-22.