hiv & aging: managing the older patient with hiv infection
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HIV & Aging: Managing the Older Patient with HIV Infection. Wayne McCormick, MD MPH 2013 AETC Asilomar Conference. HIV & Aging Consensus Panel. American Geriatrics Society American Academy of HIV Medicine AIDS Community Research Initiative of America J Applebaum [FSU], W McCormick [UW] - PowerPoint PPT PresentationTRANSCRIPT
HIV & Aging: Managing the Older Patient with HIV Infection
Wayne McCormick, MD MPH2013 AETC Asilomar Conference
HIV & Aging Consensus Panel
American Geriatrics SocietyAmerican Academy of HIV Medicine
AIDS Community Research Initiative of America
J Applebaum [FSU], W McCormick [UW] C Abrass [UW], C Boyd [JHU], S Braithwaite [NYU], VC Broudy [UW]
K Covinsky [UCSF], K Crothers [UW], R Harrington [UW], K Gebo [JHU]K Goodkin [UCLA], R Havlik [NIA], W Hazzard [UW], K High [WFU]P Hsue [UCSF], M John [UCSF], A Justice [Yale], I McNicholl [UCSF]
A Newman [Pitt], M Simone [Harvard], D Spach [UW], V Valcour [UCSF]
Case
60 yo man HIV [X24y], Hx NHL, CAP depression, Afib, OSA, hyperlipidemia, hypothyroidism, HBP, DMII ,obesity, smokes 1 pack/week
Diltiazem 240 mg QD / Lisinopril 2.5 mg QD / Warfarin 5 mg QD / Oxycodone 10 mg QID / Citalopram 20 mg QD / Metformin 500 mg BID / Levothyroxine 0.1 mg QD / Atazanavir+Ritonivir BID / Efavirenz/Emtricitibine/Tenofovir QD
Case
Exam: 220# , lungs clear, Cor irreg VR 88 Abd considerable obesity, lipodystrophyCD4 = 177, VL undetectableFBS 280, A1C = 9.2, TSH 4cholesterol 280, LDL 190
Recommended: Statins, Insulin
Case
Refused insulin.Started rosuvastatin after consulting with
pharmacist, noting drug interaction w ARV.
2 months later: More depressed.Weight gain to 244 #.
Case
Cholesterol 498Triglycerides 8700A1C 10
Psychiatry, SW involved.
Case
Engaged in exercise (walking an hour a day) and naturopathic nutritional assessment and diet change: Subsequent weight in 5 months was 200# – FBS now 110, A1C 6.4
TG 660, Cholesterol 202, LDL 110Still smoking rarely
HIV & Aging Consensus Panel
American Geriatrics SocietyAmerican Academy of HIV Medicine
AIDS Community Research Initiative of America
16 Panel Members – content consensus, section authorsModified Delphi Technique
Meeting Washington DC 11/11White House Conference 11/11
5 Staff from AGS / AAHIVM / ACRIA helped6 Reviewers – reviewed document for face validity
Objectives• Review Current Knowledge about HIV in older
patients (Epidemiology, Clinical Outcomes w ART)• Discuss Aging Phenomena in HIV (T-cell Senescence,
Multi-Morbidity, Aging [or Inflammatory] Acceleration, Frailty)• Cancer, CAD, & Advent of Non-AIDS health-
related conditions in older patients with HIV• Psychosocial Issues / Advance Directives• Review findings of the Consensus Panel
Faces of HIV
Photos courtesy of New York Magazine, Nov 2009
Photos courtesy of New York Magazine, Nov 2009
Enrico McLaneAge: 52 HIV: 17 years Short-term memory loss two hip replacements
Norma Martinez. Age: 61
HIV: 12 years lipodystrophy, fatigue
Cesar Figueroa /Age: 50 / HIV: 20 years dementia, neuropathy, depression
Mike Weyand. Age: 58 / HIV: 20 years / osteoporosis, lipodystrophy, memory loss
Joe WestmorelandAge: 53
HIV: 27 years memory loss, fatigue,
peripheral neuropathy in feet and hands
Doug TurkingtonAge: 52 HIV: 20 years osteoporosis, two hip replacements.
NA-ACCORDNorth American AIDS Cohort Collaboration on Research and Design
Age US NA-ACCORD
18-19 3764 3820-24 21197 46825-29 39603 116430-34 54895 186335-39 83935 312840-44 121465 476545-49 128546 545550-54 94957 423655-59 57359 265860-64 28141 1345>64 22103 910
US Trends in ARV Use AIM 157:325-35, 2012
Clinical Outcomes in Older Patients Treated with ART
• Virologic Suppression• Immunologic Response• Mortality
Percent with VL suppression across time by Age
6 months 12 months 18 months 24 months60%
65%
70%
75%
80%
85%
90%
95%
100% 18-<30 years 30-<40 years 40-<50 years
50-<60 years ≥60 years
Months since ART initiation
Althoff IEDEA Feb 2010
Percent with VL suppression across time by Age group and Regimen
PIs
6 months 12 months 18 months 24 months60%
65%
70%
75%
80%
85%
90%
95%
100%
18-<30 years 30-<40 years 40-<50 years50-<60 years ≥60 years
NNRTIS
6 months
12 months
18 months
24 months
60%
65%
70%
75%
80%
85%
90%
95%
100%
Althoff K IEDEA Feb 2010
Mean Increase in CD4 by Age 2 years after HAART
6 months 12 months 18 months 24 months0
50
100
150
200
250 18-<30 years 30-<40 years 40-<50 years 50-<60 years≥60 years
Months since ART initiation
Althoff K IEDEA Feb 2010
Mean Increase in CD4 by age and regimen
Boosted PIs NNRTIs
6 months 12 months 18 months 24 months0
50
100
150
200
250
18-<30 years 30-<40 years40-<50 years 50-<60 years≥60 years
6 months 12 months
18 months
24 months
0
50
100
150
200
250
Decline in Naïve T cell (CD4 and CD8) Compartment with Age
Slide courtesy Jorg Goronzy, MD
Increased “senescent” T cells, particularly CD8; indicated by lack of CD28 expression
Slide courtesy Jorg Goronzy, MD
% of CD8 cells that are CD28 negative highly correlated with influenza vaccine response
Slide courtesy Jorg Goronzy, MD
Aging Reduces T cell Diversity
Slide courtesy Jorg Goronzy, MD
Immunosenescence• Immune system in older persons
– Increased populations of terminally differentiated CD8 cells (CD28 negative)
– Reduced level of naïve CD4 and CD8 cells, with reduced T cell proliferation
– Increased T cell activation, with increased levels of inflammatory markers
– Thymic insufficiency / failure• All are accelerated in HIV
Residual Viral ReplicationPersistent virus expression (in LN)
Collagen DepositionMicrobial Translocation
High pathogen load (CMV, HCV)Thymic dysfunction
Residual Inflammation
Suboptimal CD4 Gains
Non-AIDS Events and Premature Mortality
Immuno-senescence
Adapted from Hsue CROI 2010
HIV Outcomes: What we Know Already
Adherence Older>Younger
HIV-1 RNA suppression Older >Younger, doesn’t vary by class
CD4 response Younger>Older Mortality Older >Younger,
usually due to non HIV causes
Non HIV Causes of Death Since ~2000
Source Of Known
Leading Causes (%) Reference
NY State Death Certificates
26% Alcohol/drug abuse (31%), CVD (24%), Cancer (21%)
Ann Intern Med 2006;145:397-406
BarcelonaDeath Certificates
60% Liver ( 23%), Infection (14%), Cancer (11%), CVD (6%)
HIV Med 2007:8;251-8
HOPSAscertainment
63% Liver (18%), CVD (18%), Pulmonary (16%), Renal (12%), GI (11%), Infection (10%) Cancer (8%)
J Acquir Immune Defic Syndr 2006;43:27-34
CascadeAscertainment
63% Liver (20%), Infections (24%), Unintentional (33%), Cancer (10%), CVD (9%)
AIDS 2006; 20;741-9
Comorbidities Among Patients With HIV
• Cancer: Non-AIDS-related malignancies• Neurologic / Cognitive Impairment• Endocrine: Early menopause, T deficiency• Bone disease: Osteoporosis / D deficiency
Llibre JM. Curr HIV Res. 2009;7(4):365-377.
Incidence of comorbidities: by age
B Haase CROI 2011
Bac
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Dea
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12
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0.5Age 50-64 yearsAge <50 years
Age 65+ years
50
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I)
Definitions
• Comorbidity: additional diseases beyond the index disease
• Multimorbidity: co-occurrence of diseases and functional consequences (the whole is worse than sum of the parts) = the aggregate burden of illness
• Age, several conditions, function/cognition
Impact of multimorbidity on 3-year decline in physical functioning
1
2
3
4
5
no dis
ease
1 dise
ase
2 dise
ases
>=3 dis
eases
OR
Kriegsman et al. J Clin Epidemiol 2004;57:55-65
Impact of multimorbidity on 3-year mortality
1
2
3
4
5
no dis
ease
1 dise
ase
2 dise
ases
>=3 dis
eases
OR
Kriegsman & Deeg. In: Autonomy and well-being in the aging population 2 (1997)
Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era*
020406080
100120
Relative Risk vs. HIV-unifected,Age-matched Controls
*Patel, et al. Ann Int Med 2008;148:728-36
Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era*
0123456789
10
Relative Risk vs. HIV-unifected,Age-matched Controls
*Patel, et al. Ann Int Med 2008;148:728-36
Interesting lack of increase in Breast or Prostate CA
Median Age of Cancer Dx in General Population, AIDS Population and Adjusted General Population
p< 0.01 (obs vs. exp) for all shown
Rectu
mAna
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Hodgk
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010203040506070
Obs Gen'lObs AIDSExp Gen'l
Shiels, et al. Ann Int Med 2010; 153: 452-60
Age at cancer diagnosis among people with AIDS and in the general population 1980-2006
Observed Expected in age adjusted group
P value
NHL 39 43 <.001Cervical 39 41 .03Rectal 46 51 .002Lung 49 53 .001Hodgkin's 41 38 <.001
Breast 44.5 45 .2Prostate 59 59 .5
Shiels CROI and AIM 2010
• For most cancers: there is no difference in age at cancer diagnosis among persons with AIDS compared to the general population.
Increasing Prevalence in Diabetes With Age in Both HIV-Infected and Non-Infected Populations
• Medi-Cal database July 1994–June 2000 examined for diabetes mellitus (DM) age-specific incidence rates (DM diagnosed by ICD-9 codes)
• 7219 HIV (61% male) and 2,792,971 non-HIV (30% male) individuals, for a total 7,101,180 person-years
Currier J et al. 9th CROI; 2002; Seattle. Abstract 677.
DM
Inci
denc
e R
ates
(per
100
per
son-
year
s)
Age Group18-24
0
2
4
6
8
10
12
14HIVNon-HIV
25-34 35-44 45-54 55-64 65+
Accelerated Coronary Aging in HIV-infected patients > age 40 (avg. ART ~ 11 yrs)
Guaraldi G, et al. Clin Inf Dis 2009;49:1756-62
Avg. vascular age 15 yrs > chronologic age
Thus:Increased Arterial Calcium
Increased Risk Factor Profiles
= Increased CAD
Back to Our Case
Risk for CVD in HIV most closely associated with age.
Most important interventions: ART and smoking cessation.
Jury out: statins, other lipid-lowering agents, ARV changes
SMART Study NEJM 355:2293, 2006DAD Study NEJM 356:1723, 2007
Commonalities in Long-standing HIV Infection and the Normal Aging Process
• Loss of Bone and Muscle Mass
• Weight Gain / Loss• Decrease in GFR• Memory Loss• Immunosenescence• Frailty• Multi-Morbidity• Poly-pharmacy
Number of non-HIV meds by age
B Haase CROI 2011
0
20
40
60
80
100
% o
f par
ticip
ants
<50 years 50-64 years 65+ years
Age
4+
3
2
1
0
Number ofco-medications
Neurologic Issues in HIV and Aging• In patients enrolled in the Hawaii Aging HIV Cohort:
– HIV-associated dementia 2x greater in subjects age ≥50 vs those age 20-39 (OR 2.13 [1.02-4.44])
– Increased Risk of HAD remains significant after adjustment for ART, HIV-1 RNA, CD4, education, race, drug use, and Beck Depression Inventory score (OR 3.26, [1.32-8.07])
Valcour Neurology 2004Ances JID 2010
Endocrinologic Morbidity• Testosterone Deficiency: 54% of HIV-infected
patients had testosterone <300 ng/dL. • Low androgen levels were associated with increasing
age, HIV+ IDU, HCV+ and use of psychotropic medications
• Menopause: Occurs at younger age in HIV infection average age 46 (IQR 39-49)
• Associated with increased symptoms of estrogen withdrawal
Klein CID 2005; Schoenbaum E CID 2005
BMD is lower and Fracture Prevalence is higher in HIV infection
Triant J Clin Endo Metab 2008
• BMD lower in HIV+ men at the femoral neck (p<.05) and lumbar spine ( p=0.06);
• Differences significant after adjusting for age, weight, race, testosterone level, and prednisone and IDU
• A 38% increase in fracture rate among HIV+ men
Arnsten AIDS 2007
Psychosocial Issues
• Isolation• Lack of support• Financial issues• DPOA / Directives
Psychosocial Issues: Advance Care Planning
• HIV, Aging, and Advance Care Planning• 238 HIV+ subjects [age 45-65]:• 47% had an Advance Directive• More likely with older, more educated subjects
• J Palliative Med 15:1124-9, 2012 U Colorado
Eras of the HIV Epidemic
Chu and Selwyn, J Urban Health. 2011 Mar 1
Things we need to study• High rates of comorbidities in older patients
– Which ones are most important and to what extent are they due to age, HIV, and ART?
• It is difficult to co-manage comorbidities and HIV together: – What’s the best timing of treating HIV and comorbid
disease? Vis a vis Statins? Osteoporosis Rx?– Managing multi-morbidity and drug-drug interactions
• We need to develop accurate treatment recommendations in older patients, or in the absence of this, best approaches
• Problem: the cohort is growing but does not exist yet
Conclusions• HIV / AIDS in US is increasingly an older population
• Compared to younger patients, older HIV patients have:– Better virologic response, Less immunologic boost,
Shortened survival
• Comorbid disease is prevalent
• Psychosocial issues and advanced directives are important, especially in the setting of multi-morbidity
Principles
• HIV: Early ART with attention to adherence, # meds
• Aging: Comorbid disease / Multimorbidity / Frailty
• HIV: Osteoporosis, Cancers, Cognition
• Aging: Psychosocial Issues / Advanced Directives
Recommendations• Start older patients with ART earlier for improved CD4
counts and reducing comorbidities– Watch closely for side effects/toxicities/polypharmacy
• Screen for comorbid disease / multimorbidity– For osteoporosis– For cancer– For STD’s
• Avoiding comorbid disease– Vaccinations– Smoking cessation, Exercise, Diet– Lipids, Hypertension, watch Creatinine Clearance
• Treat Comorbid:– Substance Abuse /Mental Health– HCV
• Address psychosocial issues and advanced directives
Resources
• http://aidsinfo.nih.gov/guidelines
• http://www.aahivm.org/hivandagingforum
• http://www.americangeriatrics.org
• Summary Report from the HIV & Aging Consensus Project: Treatment Strategies for Clinicians Managing Older Individuals with HIV Infection. JAGS 60:974-9, 2012
• Patient-Centered Care for Older Adults with Multiple Chronic Conditions. JAGS 60:1957-68, 2012
Management: effect of vitamin D on Postural Sway
Usual diet Alfacalcidol treatment
Fujita et al, 2004 ASBMR Annual Meeting
Significant difference in tract of center of gravity (p 0.0039)