HIV & Aging: Cases...HIV & Aging: Cases Wayne McCormick February 2017 Case 78 yo man HIV [X28y], Hx weight loss and insidious cognitive impairment over the past few years, word-finding

HIV & Aging: Cases

Wayne McCormick

February 2017

Case

78 yo man HIV [X28y], Hx weight loss and insidious cognitive impairment over the past few years, word-finding deficit

CBC Hct 30, Cr 2, CD4 82, VL 280K, CT OKAdmitted to Memory Unit ALF, started on

meds

Integrase Inhibitor / dual NRTI QD

HIV (McCormick), NW Gwec Winter 2017 1

Case

Slow steady improvement in weight, function, word-finding

Difficulties ongoing with problem-solving

CD4 at one year 152, VL undet

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


Percent with VL suppression across time by Age

60%

65%

70%

75%

80%

85%

90%

95%

100%

6 months 12 months 18 months 24 months

Months since ART initiation

18-<30 years 30-<40 years 40-<50 years

50-<60 years ≥60 years

Althoff IEDEA Feb 2010

Percent with VL suppression across time by Age group and Regimen

PIs

60%

65%

70%

75%

80%

85%

90%

95%

100%


18-<30 years 30-<40 years 40-<50 years

50-<60 years ≥60 years

NNRTIS

60%

65%

70%

75%

80%

85%

90%

95%

100%

6months

12months

18months

24months

Althoff K IEDEA Feb 2010


Mean Increase in CD4 by Age 2 years after HAART

0

50

100

150

200

250


Months since ART initiation

18-<30 years 30-<40 years 40-<50 years50-<60 years ≥60 years

Althoff K IEDEA Feb 2010

Mean Increase in CD4 by age and regimen

Boosted PIs NNRTIs

0

50

100

150

200

250


18-<30 years 30-<40 years

40-<50 years 50-<60 years

≥60 years

0

50

100

150

200

250



Case

82 yo man HIV [X30y], Hx alcoholism, CAD/MI, COPD, and insidious but progressive cognitive impairment over the past few years

Partner died 30 years agoHad a fall with a fractured humerus last year

Atenolol 40 mg QD / Lisinopril 2.5 mg QD / ASA 81 mg QD / Integrase Inhibitor / dual NRTI QD – religiously adherent to meds for years

Case

Exam – thin tall man NAD, MMSE 22

MRI – volume lossCD4 380 (was as high as 750 a decade ago)VL undetOther labs ok; CBC, CMP, TSH, B12, VDRL


Case

What is the cause of his cognitive impairment?

Multi-factorial Dementia

Most cases of dementia in older persons are multi-factorial.Since Alzheimer’s disease is most common, it is usually a co-

factor.Other common co-factors include vascular disease and

alcoholism.Frailty, sensory impairment, and nutritional deficiency often

exacerbate dementia symptomatology.


Case

What is the cause of his falls?

Syndromes

In geriatrics, seldom is there ONE cause of any phenomenon.

We cannot apply OCCAM’s razor to our diagnostic thinking.

We have to learn how to think “SYNDROMICALLY”.


Multifactorial causes and potential contributors to

falls in the elderly

Frailty

Frailty =

Weakness (decreased grip strength)Slowness (gait – observed get up and go)Decreased activity (subjective)Low energy / lassitudeUnintended weight loss

Constellation of 3 or more, gestalt


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

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 /

DOSS 100 mg BID / Senna 1 tab QD / Integrase Inhibitor QD / dual NRTI 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


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

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%), Pulmonary (16%), Renal (12%), GI (11%), Infection (10%) Cancer (8%)

J Acquir Immune Defic Syndr 2006;43:27-34

Cascade

Ascertainment

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.


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

OR

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


Impact of multimorbidity on 3-year mortality

1

2

3

4

5

OR

Kriegsman & Deeg. In: Autonomy and well-being in the aging population 2 (1997)

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

Inc

iden

ce R

ates

(per

100

per

son-

year

s)

Age Group

18-240

2

4

6

8

10

12

14HIVNon-HIV

25-34 35-44 45-54 55-64 65+


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%

of p

artic

ipan

ts

<50 years 50-64 years 65+ years

Age

4+

3

2

1

0

Number ofco-medications

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 /

DOSS 100 mg BID / Senna 1 QD / Integrase Inhibitor QD / dual NRTI QD


Case

How do you go about negotiating med reconciliation in older patients on a dozen or more medications?

Case

Polypharmacy reduction – has to be very individualized

Most people have a very hard time taking this many meds. Which of these meds are you not taking?

Of the ones you are taking, which ones would you like to stop?

Would you like suggestions from me about which ones to stop?


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

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)


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


Documents

HIV & Aging: Cases...HIV & Aging: Cases Wayne McCormick February 2017 Case 78 yo man HIV [X28y], Hx weight loss and insidious cognitive impairment over the past few years, word-finding