HIV & Aging: Managing the Older Patient with HIV Infection

53
HIV & Aging: Managing the Older Patient with HIV Infection Wayne McCormick, MD MPH 2013 AETC Asilomar Conference

description

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 Presentation

Transcript of HIV & Aging: Managing the Older Patient with HIV Infection

Page 1: HIV & Aging: Managing the Older Patient with HIV Infection

HIV & Aging: Managing the Older Patient with HIV Infection

Wayne McCormick, MD MPH2013 AETC Asilomar Conference

Page 2: HIV & Aging: Managing the Older Patient with HIV Infection

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]

Page 3: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 4: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 5: HIV & Aging: Managing the Older Patient with HIV Infection

Case

Refused insulin.Started rosuvastatin after consulting with

pharmacist, noting drug interaction w ARV.

2 months later: More depressed.Weight gain to 244 #.

Page 6: HIV & Aging: Managing the Older Patient with HIV Infection

Case

Cholesterol 498Triglycerides 8700A1C 10

Psychiatry, SW involved.

Page 7: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 8: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 9: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 10: HIV & Aging: Managing the Older Patient with HIV Infection

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.

Page 11: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 12: HIV & Aging: Managing the Older Patient with HIV Infection
Page 13: HIV & Aging: Managing the Older Patient with HIV Infection

Clinical Outcomes in Older Patients Treated with ART

• Virologic Suppression• Immunologic Response• Mortality

Page 14: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 15: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 16: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 17: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 18: HIV & Aging: Managing the Older Patient with HIV Infection

Decline in Naïve T cell (CD4 and CD8) Compartment with Age

Slide courtesy Jorg Goronzy, MD

Page 19: HIV & Aging: Managing the Older Patient with HIV Infection

Increased “senescent” T cells, particularly CD8; indicated by lack of CD28 expression

Slide courtesy Jorg Goronzy, MD

Page 20: HIV & Aging: Managing the Older Patient with HIV Infection

% of CD8 cells that are CD28 negative highly correlated with influenza vaccine response

Slide courtesy Jorg Goronzy, MD

Page 21: HIV & Aging: Managing the Older Patient with HIV Infection

Aging Reduces T cell Diversity

Slide courtesy Jorg Goronzy, MD

Page 22: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 23: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 24: HIV & Aging: Managing the Older Patient with HIV Infection
Page 25: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 26: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 27: HIV & Aging: Managing the Older Patient with HIV Infection

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.

Page 28: HIV & Aging: Managing the Older Patient with HIV Infection

Incidence of comorbidities: by age

B Haase CROI 2011

Bac

teria

l pne

umon

ia

Cer

ebra

l inf

arct

ion

Cor

onar

y an

giop

last

y

Myo

card

ial i

nfar

ctio

n

Pro

cedu

res

on o

ther

arte

ries

Pul

mon

ary

embo

lism

Frac

ture

, ade

quat

e tra

uma

Frac

ture

, ina

dequ

ate

traum

a

Ost

eopo

rosi

s

Dia

bete

s m

ellit

us

Non

AID

S d

efin

ing

mal

igna

ncie

s

AID

S d

efin

ing

even

t

Dea

th

12

51020

0.10.2

0.5Age 50-64 yearsAge <50 years

Age 65+ years

50

Inci

denc

epe

r 100

0 py

rs (9

5% C

I)

Page 29: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 30: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 31: HIV & Aging: Managing the Older Patient with HIV Infection

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)

Page 32: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 33: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 34: HIV & Aging: Managing the Older Patient with HIV Infection

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

l

Lary

nxLu

ng

Hodgk

in's

Mye

loma

010203040506070

Obs Gen'lObs AIDSExp Gen'l

Shiels, et al. Ann Int Med 2010; 153: 452-60

Page 35: HIV & Aging: Managing the Older Patient with HIV Infection

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.

Page 36: HIV & Aging: Managing the Older Patient with HIV Infection

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+

Page 37: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 38: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 39: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 40: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 41: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 42: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 43: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 44: HIV & Aging: Managing the Older Patient with HIV Infection

Psychosocial Issues

• Isolation• Lack of support• Financial issues• DPOA / Directives

Page 45: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 46: HIV & Aging: Managing the Older Patient with HIV Infection

Eras of the HIV Epidemic

Chu and Selwyn, J Urban Health. 2011 Mar 1

Page 47: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 48: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 49: HIV & Aging: Managing the Older Patient with HIV Infection

Principles

• HIV: Early ART with attention to adherence, # meds

• Aging: Comorbid disease / Multimorbidity / Frailty

• HIV: Osteoporosis, Cancers, Cognition

• Aging: Psychosocial Issues / Advanced Directives

Page 50: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 51: HIV & Aging: Managing the Older Patient with HIV Infection

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

Page 52: HIV & Aging: Managing the Older Patient with HIV Infection
Page 53: HIV & Aging: Managing the Older Patient with HIV Infection

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)