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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]

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hiv aging managing the older patient with hiv infection
HIV & Aging: Managing the Older Patient with HIV Infection

Wayne McCormick, MD MPH

2013 AETC Asilomar Conference

hiv aging consensus panel
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]

slide3
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

slide4
Case

Exam: 220# , lungs clear, Corirreg VR 88

Abd considerable obesity, lipodystrophy

CD4 = 177, VL undetectable

FBS 280, A1C = 9.2, TSH 4

cholesterol 280, LDL 190

Recommended: Statins, Insulin

slide5
Case

Refused insulin.

Started rosuvastatin after consulting with pharmacist, noting drug interaction w ARV.

2 months later: More depressed.

Weight gain to 244 #.

slide6
Case

Cholesterol 498

Triglycerides 8700

A1C 10

Psychiatry, SW involved.

slide7
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 panel1
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
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
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

Photos courtesy of New York Magazine, Nov 2009

Cesar Figueroa /Age: 50 / HIV: 20 years

dementia, neuropathy, depression

Photos courtesy of New York Magazine, Nov 2009

na accord north american aids cohort collaboration on research and design
NA-ACCORDNorth American AIDS Cohort Collaboration on Research and Design

Age US NA-ACCORD

18-19 3764 38

20-24 21197 468

25-29 39603 1164

30-34 54895 1863

35-39 83935 3128

40-44 121465 4765

45-49 128546 5455

50-54 94957 4236

55-59 57359 2658

60-64 28141 1345

>64 22103 910

US Trends in ARV Use AIM 157:325-35, 2012

clinical outcomes in older patients treated with art
Clinical Outcomes in Older Patients Treated with ART
  • Virologic Suppression
  • Immunologic Response
  • Mortality
percent with vl suppression across time by age group and regimen
Percent with VL suppression across time by Age group and Regimen

PIs

NNRTIS

Althoff K IEDEA Feb 2010

increased senescent t cells particularly cd8 indicated by lack of cd28 expression
Increased “senescent” T cells, particularly CD8; indicated by lack of CD28 expression

Slide courtesy JorgGoronzy, MD

of cd8 cells that are cd28 negative highly correlated with influenza vaccine response
% of CD8 cells that are CD28 negative highly correlated with influenza vaccine response

Slide courtesy JorgGoronzy, MD

aging reduces t cell diversity
Aging Reduces T cell Diversity

Slide courtesy Jorg Goronzy, MD

immunosenescence
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
slide23

Residual Viral Replication

Persistent virus expression (in LN)

Collagen Deposition

Microbial Translocation

High pathogen load (CMV, HCV)

Thymic dysfunction

Residual Inflammation

Immuno-senescence

Suboptimal CD4 Gains

Non-AIDS Events and Premature Mortality

Adapted from Hsue CROI 2010

comorbidities among patients with hiv
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

50

20

10

5

per 1000 pyrs (95% CI)

Incidence

2

1

0.5

Age 65+ years

Age 50-64 years

0.2

Age <50 years

0.1

Death

Osteoporosis

Diabetes mellitus

Cerebral infarction

AIDS defining event

Bacterial pneumonia

Myocardial infarction

Pulmonary embolism

Coronary angioplasty

Fracture, adequate trauma

Fracture, inadequate trauma

Procedures on other arteries

Non AIDS defining malignancies

Incidence of comorbidities: by age

B Haase CROI 2011

definitions
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
Impact of multimorbidity on 3-year decline in physical functioning

Kriegsman et al. J Clin Epidemiol 2004;57:55-65

impact of multimorbidity on 3 year mortality
Impact of multimorbidity on 3-year mortality

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
Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era*

*Patel, et al. Ann Int Med 2008;148:728-36

incidence of cancer in hiv infected persons in the post haart era1
Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era*

Interesting lack of increase in Breast or Prostate CA

*Patel, et al. Ann Int Med 2008;148:728-36

slide34
Median Age of Cancer Dx in General Population, AIDS Population and Adjusted General Populationp< 0.01 (obs vs. exp) for all shown

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
Age at cancer diagnosis among people with AIDS and in the general population 1980-2006
  • 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
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

14

HIV

12

Non-HIV

10

8

DM Incidence Rates

(per 100 person-years)

6

4

2

0

18-24

25-34

35-44

45-54

55-64

65+

Age Group

Currier J et al. 9th CROI; 2002; Seattle. Abstract 677.

accelerated coronary aging in hiv infected patients age 40 avg art 11 yrs
Accelerated Coronary Aging in HIV-infected patients > age 40 (avg. ART ~ 11 yrs)

Avg. vascular age 15 yrs > chronologic age

Thus:

Increased Arterial Calcium

Increased Risk Factor Profiles

= Increased CAD

Guaraldi G, et al. ClinInfDis 2009;49:1756-62

back to our case
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
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

100

Number of

co-medications

80

0

60

% of participants

1

40

2

3

20

4+

0

<50 years

50-64 years

65+ years

Age

Number of non-HIV meds by age

B Haase CROI 2011

neurologic issues in hiv and aging
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
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 p revalence is higher in hiv infection
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

slide44

Psychosocial Issues

  • Isolation
  • Lack of support
  • Financial issues
  • DPOA / Directives
slide45

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
Eras of the HIV Epidemic

Chu and Selwyn, J Urban Health. 2011 Mar 1

things we need to study
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
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
Principles
  • HIV: Early ART with attention to adherence, # meds
  • Aging: Comorbid disease / Multimorbidity / Frailty
  • HIV: Osteoporosis, Cancers, Cognition
  • Aging: Psychosocial Issues / Advanced Directives
recommendations
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
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
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