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.