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]
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, lipodystrophy
CD4 = 177, VL undetectable
FBS 280, A1C = 9.2, TSH 4
cholesterol 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 498
Triglycerides 8700
A1C 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 110
Still smoking rarely
HIV & Aging Consensus Panel
American Geriatrics Society
American Academy of HIV Medicine
AIDS Community Research Initiative of America
16 Panel Members – content consensus, section authors
Modified Delphi Technique
Meeting Washington DC 11/11
White House Conference 11/11
5 Staff from AGS / AAHIVM / ACRIA helped
6 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 healthrelated conditions in older patients with HIV
• Psychosocial Issues / Advance Directives
• Review findings of the Consensus Panel
Faces of HIV
Norma Martinez.
Age: 61
HIV: 12 years
lipodystrophy, fatigue
Doug Turkington
Age: 52
HIV: 20 years
osteoporosis, two hip replacements.
Enrico McLane
Age: 52
HIV: 17 years
Short-term memory loss
two hip replacements
Joe Westmoreland
Age: 53
HIV: 27 years
memory loss, fatigue,
peripheral neuropathy
in feet and hands
Mike Weyand. Age: 58 / HIV: 20 years /
osteoporosis, lipodystrophy, memory loss
Cesar Figueroa /Age: 50 / HIV: 20 years
dementia, neuropathy, depression
Photos courtesy of New York Magazine, Nov 2009
Photos courtesy of New York Magazine, Nov 2009
NA-ACCORD
North American AIDS Cohort Collaboration on Research and Design
Age
18-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
>64
US
3764
21197
39603
54895
83935
121465
128546
94957
57359
28141
22103
US Trends in ARV Use
NA-ACCORD
38
468
1164
1863
3128
4765
5455
4236
2658
1345
910
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
100%
18-<30 years
30-<40 years
95%
50-<60 years
≥60 years
40-<50 years
90%
85%
80%
75%
70%
65%
60%
6 months
12 months
18 months
Months since ART initiation
Althoff IEDEA Feb 2010
24 months
Percent with VL suppression across time
by Age group and Regimen
100%
100%
PIs
95%
95%
90%
90%
85%
85%
80%
80%
75%
75%
70%
70%
65%
65%
60%
60%
6 months
12 months
18 months
18-<30 years
30-<40 years
50-<60 years
≥60 years
Althoff K IEDEA Feb 2010
24 months
40-<50 years
NNRTIS
6
12
18
24
months months months months
Mean Increase in CD4 by Age
2 years after HAART
250
18-<30 years
50-<60 years
30-<40 years
≥60 years
40-<50 years
200
150
100
50
0
6 months
12 months
18 months
Months since ART initiation
Althoff K IEDEA Feb 2010
24 months
Mean Increase in CD4 by age and regimen
Boosted PIs
NNRTIs
250
250
200
200
150
150
100
100
50
50
0
0
6 months 12 months 18 months 24 months
18-<30 years
40-<50 years
≥60 years
30-<40 years
50-<60 years
6 months 12 months 18 months 24 months
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
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 Replication
Persistent virus expression (in LN)
Collagen Deposition
Microbial Translocation
High pathogen load (CMV, HCV)
Thymic dysfunction
Suboptimal
CD4 Gains
Residual
Inflammation
Immunosenescence
Non-AIDS Events and Premature Mortality
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
Leading Causes (%)
Known
Reference
NY State
Death Certificates
26%
Alcohol/drug abuse (31%), CVD
(24%), Cancer (21%)
Ann Intern Med
2006;145:397406
Barcelona
Death Certificates
60%
Liver ( 23%), Infection (14%),
Cancer (11%), CVD (6%)
HIV Med
2007:8;251-8
HOPS
Ascertainment
63%
Liver (18%), CVD (18%),
J Acquir
Pulmonary (16%), Renal (12%), GI Immune Defic
(11%), Infection (10%) Cancer (8%) Syndr
2006;43:27-34
Cascade
Ascertainment
63%
Liver (20%), Infections (24%),
AIDS 2006;
Unintentional (33%), Cancer (10%), 20;741-9
CVD (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.
Death
AIDS defining event
0.2
Non AIDS defining malignancies
0.5
Diabetes mellitus
Osteoporosis
Fracture, inadequate trauma
Fracture, adequate trauma
Pulmonary embolism
Procedures on other arteries
Myocardial infarction
Coronary angioplasty
Cerebral infarction
Bacterial pneumonia
Incidence
per 1000 pyrs (95% CI)
Incidence of comorbidities: by age
50
20
10
5
2
1
Age 65+ years
Age 50-64 years
Age <50 years
0.1
B Haase CROI 2011
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
OR 5
4
3
2
as
es
di
se
>=
3
2
di
se
a
se
s
se
di
se
a
1
no
di
se
as
e
1
Kriegsman et al. J Clin Epidemiol 2004;57:55-65
Impact of multimorbidity
on 3-year mortality
OR 5
4
3
2
as
es
di
se
>=
3
2
di
se
a
se
s
se
di
se
a
1
no
di
se
as
e
1
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*
Relative Risk vs. HIV-unifected,
Age-matched Controls
120
100
80
60
40
20
gk
in
's
Dz
H
L
H
od
*Patel, et al. Ann Int Med 2008;148:728-36
N
An
al
KS
0
Incidence of Cancer in HIV-Infected Persons
in the Post-HAART Era*
Relative Risk vs. HIV-unifected,
Age-matched Controls
*Patel, et al. Ann Int Med 2008;148:728-36
st
at
e
Pr
o
re
as
t
B
Lu
Li
ve
r
ng
M
el
an
H
om
ea
d
a
an
d
N
ec
k
C
ol
or
ec
ta
l
C
er
vi
ca
l
10
9
8
7
6
5
4
3
2
1
0
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
70
60
50
40
30
20
10
0
Shiels, et al. Ann Int Med 2010; 153: 452-60
Obs Gen'l
Obs AIDS
Exp Gen'l
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
<.001
Cervical
39
41
.03
Rectal
46
51
.002
Lung
49
53
.001
Hodgkin's
41
38
<.001
Breast
44.5
45
.2
Prostate
59
59
.5
• For most
cancers: there is
no difference in
age at cancer
diagnosis among
persons with
AIDS compared
to the general
population.
Shiels CROI and AIM 2010
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
DM Incidence Rates
(per 100 person-years)
14
12
HIV
Non-HIV
10
8
6
4
2
0
18-24
25-34
35-44
45-54
Age Group
Currier J et al. 9th CROI; 2002; Seattle. Abstract 677.
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
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, 2006
DAD 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
% of participants
100
Number of
co-medications
80
0
60
1
40
2
3
20
4+
0
<50 years 50-64 years
65+ years
Age
B Haase CROI 2011
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 2004
Ances 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
• 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
Triant J Clin Endo Metab 2008
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
Significant difference in tract of center of gravity (p 0.0039)
Usual diet
Alfacalcidol treatment
Fujita et al, 2004 ASBMR Annual Meeting