HIV and Aging

Kathleen K Casey, MD Director, AIDS Ambulatory Care CenterJersey Shore University Medical Center

2

1718.8

20.5 21.523.4

25.427.4

0

5

10

15

20

25

30

2001 2002 2003 2004 2005 2006 2007

% o

f Pati

ents

50

and

Old

er

Estimated Percentage of Persons Living with HIV/AIDS Who Are 50 and Older by Year, 2001-2007a

Yeara For years 2001-2003, data are based on 33 states and US-dependent areas with confidential name-based HIV infection reporting, CDC HIV/AIDS Surveillance Report, 2005. For years 2004-2007, data are based on 34 states and 5 US-dependent areas with confidential name-based HIV infection reporting, CDC HIV/AIDS Surveillance Report, 2007.

Gay Men’s Health Crisis. Growing Older With the Epidemic: HIV and Aging. 2010.

Concurrent HIV/AIDS Among Persons Diagnosed with HIV in the United States in 2006, by Age Group

3

Pers

ons

New

ly D

iagn

osed

with

H

IV, %

HIV only (non-AIDS) Concurrent HIV/AIDS

12 20 2438 44 49 55

7662 56 51 45

30

20

10

0

40

50

60

70

80

90

100

0-12 13-19 20-29 30-39 40-49 50-59 60+Age Group at Diagnosis

a AIDS diagnosis within one year of HIV diagnosis.Gay Men’s Health Crisis. Growing Older With the Epidemic: HIV and Aging. 2010.

88 80

How Are We Finding Our Patients Over 50?

• Hospitalized patients with opportunistic infections• Screening of patients with malignancy• Partner Testing• STD clinic visits• Dialysis Screening• Dementia screening• Rarely through routine primary care assessment

and routine testing despite CDC recommendations!

• Older patients are more likely than younger patients to present late for HIV diagnosis and care1

• Physicians are less likely to discuss HIV/AIDS and related risk factors with older patients2

• Asymptomatic older HIV-infected individuals are less likely to seek out testing and medical care3

• Symptomatic older HIV-infected individuals are more likely to attribute HIV-related symptoms to other illnesses or to the normal aging process3

5

1 Cuzin L et al. Clin Infect Dis. 2007;45:654-657. 2 Skiest DJ et al. Arch Fam Med. 1997;6:289-294.3 Siegel K et al. AIDS Care. 1999;11:525-535.

• Physicians reported that 69.7% of their patients older than 50 years rarely or never asked them questions about HIV or AIDS

• 60.8% of respondents reported rarely or never discussing HIV or AIDS with their patients aged >50 years, while 40% reported rarely or never asking their patients aged >50 years about possible HIV risk factors

• 67.5% of respondents reported rarely or never discussing behaviors that may reduce HIV risk in their patients older than 50 years, while only 6.8% of the physicians rarely or never discussed risk factors in their patients younger than 30 years

• Family practitioners were more likely than internists to rarely or never ask patients aged >50 years about HIV risk factors (54.9% vs 28.9%, P=.007)

6Skiest DJ et al. Arch Fam Med. 1997;6:289-294.

• Study explored how symptom interpretations influence the initiation of HIV testing and medical care among adults aged ≥50 years through patient interviews

• N=78 patients living with HIV (58 men, 20 women)• 19 patients aged ≥60• 32 African American, 15 Puerto Rican, 31 non-Hispanic whites• 51% identified as completely/mostly heterosexual, 42% as completely/mostly homosexual• 47 (60%) diagnosed with AIDS, 9 (12%) symptomatic HIV disease, 22 (28%) asymptomatic HIV infection• Mean CD4 cell count at first interview: 400 cells/mm3 (SD=311, range 32-1500 cells/mm3)• 91% reported other chronic health conditions: heart disease (27%), respiratory problems (36%), arthritis

(36%), and other illnesses (41%)

• Presence or absence of putative symptoms of AIDS most often led to patients’ HIV testing

• Attributing symptoms to other illnesses (eg, hypertension, normal aging, menopause) was a common reason for delaying HIV testing

• Some patients delayed or refused to seek medical care even after being diagnosed as HIV+ because they did not feel ill and/or misattributed their symptoms to other illnesses

7Siegel K et al. AIDS Care. 1999;11:525-535.

How well do older patients do with HIV treatment?

0

0.2

0.4

0.6

0.8

1

1.2

9

Achieving HIV RNA<500 Copies/mL at 12 Months

Experiencing HIV RNARebound Within 2 Years

a P =.009; b P =.01. Adjusted for age only.

Haz

ard

Ratio

(95%

CI)

18-39

1.00(Reference)

40-49 ≥50

Age at Baseline (years)

0.81b

(0.69-0.96)

0.88(0.73-1.06)

CI, confidence interval.Silverberg MJ et al. Arch Intern Med. 2007;167:684-691.

0

0.2

0.4

0.6

0.8

1

1.2

18-39 40-49 ≥50

Age at Baseline (years)

1.00(Reference)

0.97(0.88-1.06)

1.15a

(1.04-1.27)

Haz

ard

Ratio

(95%

CI)

• Patients 50 years and older have higher risk of clinical progression but improved virologic response compared with younger patients

• Prospective cohort study of 3015 treatment-naive patients initiating ART• 50 years and older: n=401• Younger than 50 years: n=2614

• Median follow-up: 31.5 months• At baseline, older patients more likely to have

• ADE (P =.0001)• Lower CD4 T-cell count (P =.0002)• Higher HIV-1 RNA level (P =.0001)

10

Outcome Adjusted HR P Value

Progression to ADE or death 1.52 .0035

Progression to new ADE 1.50 .0087

HIV-1 RNA <500 copies/mL 1.23 <.05ADE, AIDS-defining event; HR, hazard ratio.

Grabar S. AIDS. 2004;18:2029-2038.

0

10

20

30

40

50

60

11

Rat

es p

er

100

0 P

erso

n-y

ears

Death AIDS-definingIllnesses

(hospitalizations)

28.8

47.4a

8.4 7.5

PCP, pneumocystis pneumonia.

Silverberg MJ et al. Arch Intern Med. 2007;167:684-691.

PCP Candidiasis AIDSDementia

WastingSyndrome

AIDS Diagnoses

28.5

36.4b

2.35.9a

1.65.9a

2.3

7.2a

a P ≤ .001 and b P=.01 vs <50 years.

Age (years) <50 (n=4094) ≥50 (n=997)

• Kaiser Permanente of Northern California chart review study of all members who initiated ART from 1995-2004 (N=5090) 18 years and older; starting 3 or more anti-retrovirals in combination; median follow-up:

3.8 years

12

18 - 39 Years 40 - 49 Years ≥50 Years

Parameter n (%) n (%)OR (95%

CI) n (%) OR (95%)

TC and LDLa

310 (21.0) 311 (26.4) 1.31 (0.84-2.06)

241 (34.0)

1.66 (1.02 - 2.70)

Glucoseb 917 (6.0) 713 (11.4) 1.92 (1.17-3.15)

486 (14.4)

2.85 (1.71 - 4.75)

Creatininec 1265 (3.2) 1021 (5.8) 1.06 (0.53-2.12)

625 (8.3) 2.03 (1.03 - 4.00)

Silverberg MJ. Arch Intern Med. 2007;167:684-691.LDL, low-density lipoprotein; NR, not reported; OR, odds ratio; TC, total cholesterol.

a Abnormal cutoff defined as ≥240 mg/dL for total cholesterol and ≥ 160 mg/dL for LDL cholesterol.b Abnormal cutoff defined as 161 mg/dL (random), 126 mg/dL (fasting) and 54 mg/dL (low).c Abnormal cutoff defined as ≥1.8 mg/dL for men and ≥1.65 mg/dL for women.

Analysis of Patients Who Developed at Least Grade 2 Laboratory Abnormality After ART Initiation

• Assessed deaths in 13 HIV-1 cohorts composed of 39,727 persons (5293 patients 50 years and older)

• Of 1876 deaths, definitive cause in 85%

• Non-AIDS–related deaths in 50.5%:

13Antiretroviral Therapy Cohort Collaboration (ART-CC). Clin Infect Dis. 2010;50:1387-1396.

InfectionNon-AIDS

16.3%

CVD15.7%

Malignancy23.5%

ViolenceSub Abuse 15.4%

Liver-related14.1%

Other 9.0%

Respiratory3.1%

Renal3.0%

• Among 2857 HIV-infected patients participating in ALLRT study1:• At baseline, 16% of patients had abnormal levels of urine protein as

measured by ratio of spot urine (P/Cr ≥0.2)• Older age was significantly associated with P/Cr ≥0.2

• Per 10 years: OR 1.21 (95% CI, 1.10-1.33; P <.001)

• In the EuroSIDA cohort, the rate of chronic renal failurea at baseline ranged from 3.5% to 4.7% depending on the method of GFR calculation2

• By multivariate analysis, age was a strong predictor of chronic renal failure at baseline

• OR 5.47, 95% CI, 4.4-6.72; P <.00012

14

a GFR <60 mL/min/1.73 m2.GFR, glomerular filtration rate.

1 Gupta SK, et al. Antivir Ther. 2009;14:543-549. 2 Mocroft A. AIDS. 2007;21:1119-1127.

• Multiple studies have found increased prevalence of osteoporosis and osteopenia in persons with HIV compared with uninfected persons2

• Meta-analysis of studies2 • 67% persons with HIV had

reduced BMD (OR 6.4)

• 15% persons with HIV had osteoporosis (OR 3.7)

15

1 Aaron JE et al. Clin Orthop Relat Res. 1987;215:260-271. 2 Brown TT et al. AIDS. 2006;20:2165-2174.

BMD Loss with Age in the General Population, by Sex1

Mean ± SE

Chan

ge in

Bon

ea Vol

ume,

%

Age (years)40 50 60 70

10

15

20

25

30

FemaleMale

n=15

n=14 n=13

n=19 n=14

n=26

n=15

n=18

n=29

n=21

0

1

2

3

4

5

6

7

30-39 40-49 50-59 60-69 70-79Age (years)

HIV+ HIV-

0

1

2

3

4

5

6

7

20-29 30-39 40-49 50-59 60-69

Age (years)

HIV+ HIV-

8525 HIV+ and 2,208,792 HIV- Patients from 1996-2008

Men

a Clinical care data registry from the Partners HealthCare System, which consists primarily of Brigham and Women’s Hospital and Massachusetts General Hospital.

Triant VA et al. J Clin Endocrinol Metab. 2008;93:3499-3504.

P =.002(overall comparison)

P <.0001(overall comparison)

Women

16

Freq

uenc

y pe

r 100

Per

sons

• In a cross-sectional analysis of 202 patients with HIV enrolled in the Hawaii Aging with HIV Cohort (n=103 patients 50 years and older):

• HIV-associated dementia was more frequent in adults aged 50 years and older vs those aged 20-39 years

• OR 2.13, 95% CI, 1.02-4.44

• After adjusting for education, race, drug use, ART status, viral load, CD4 count, and Beck Depression Inventory score, risk of HIV-associated dementia was even higher among older patients

• OR 3.26, 95% CI, 1.32-8.07

17Valcour VG et al. Neurology. 2004;63:822-827.

Cancer Type

Cancer Diagnosis (Mean Age SD)

P ValueHIV+a HIV-b

Anal/rectal SCC 51.65 8.66 57.53 15.93 .0001

Hodgkin lymphoma 39.66 7.80 41.42 17.87 .685

Non-Hodgkin lymphoma

41.54 9.20 65.56 16.17 .0001

Cervical 41.94 5.29 51.20 17.87 .053

Liver 40.94 6.39 65.36 14.86 .0001

Head and neck 50.67 11.58 67.11 13.44 .0001

Lung 51.65 8.66 68.81 12.52 .0001

Breast 44.92 12.00 60.57 10.25 .0001

Prostate 53.46 12.72 71.48 15.98 .0001

Nguyen ML et al. 18th IAC; Vienna; 2010. Abstract WEAB0105.18

ADM, AIDS-defining malignancy; NADM, non-AIDS—defining malignancy; SCC, squamous cell carcinoma.

a N=8300 patients seen at the Infectious Diseases Ponce de Leon Center during 2000-2007 (516 cancer cases).b Data gathered from 17 registries of the Surveillance, Epidemiology and End Results (SEER) database.

19Adapted from Grunfeld C et al. Circulation. 2008;118:e20-e28.

Insulin resistance↑ Glucose

Dyslipidemia:↑ TG↓ HDL↑ FFA↑ Small, dense LDL↕↔ LDL

CVD

Inflammation

Body composition:•Lipoatrophy•Lipohypertrophy

ART, antiretroviral therapy; ARV, antiretroviral; FFA, free fatty acids; HDL, high-density lipoprotein; HTN, hypertension; LDL, low-density lipoprotein; TG, triglycerides.

Predisposing factors:•Genetics, smoking, sedentary lifestyle, diet, obesity, HTN, renal disease

HIV infection ART, including specific ARVs

20

b

b

b

Adapted from Triant VA et al. Clin Endocrinol Metab. 2007;92:2506-2512.

a Cohort population: all patients aged 18-84 years who presented on at least two occasions to one of two Boston health care facilities, Brigham and Women’s Hospital (BWH) or Massachusetts General Hospital (MGH) between 1996 and 2004.

b P <.0001 for comparison between proportions in HIV+ and HIV- cohorts by Χ2.

Patie

nts,

%

Percentage of Subjects with CV Risk Factors by ICD Code

ICD, International Classification of Disease(s).

21Triant VA et al. J Clin Endocrinol Metab. 2007;92:2506-2512.

AMI Rates by Age Group

0

20

40

60

80

100

18-34 35-44 45-54 55-64 65-74

Even

ts p

er 1

000

P-Y

Age Group (years)

HIV+ (n = 3851) HIV- (n = 1,044,589)

AMI, acute myocardial infarction; P-Y, patient-year.

a Clinical care data registry from the Partners HealthCare System, which consists primarily of Brigham and Women’s Hospital and Massachusetts General Hospital; identified patients who presented at least twice from 1996-2004.

Framingham Cardiovascular Risk Assessment Tool• Age• Gender• Total cholesterol• HDL• Smoking status• Systolic blood pressure• Family history of CAD• Medication used to control blood pressure

BMI, body mass index; CHD, coronary heart disease; D:A:D, data collection on adverse events of anti-HIV drugs.

Adapted from Friis-Møller N et al. AIDS. 2003;17:1179-1193.

• Large observational cohort of HIV+ patients followed longitudinally (N = 17,852)

• 15,537 (87%) with previous ART exposure; 2315 (13%) ARV-naive

23

11.4

1.4

51.5

3.58.5

2.5

22.2

33.8

0

10

20

30

40

50

60

Perc

enta

ge o

f Coh

ort w

ith

Risk

Fac

tor a

t Bas

elin

e

Family Historyof CHD

PreviousCVD

CurrentSmoking

BMI>30 mg/m2

HTN DiabetesMellitus

↑TotalCholesterol

↑TG

• HIV+ treatment-naïve patients with undetectable VLs (HIV controllers) had a higher mean carotid IMT than the HIV- participants, even after controlling for traditional risk factors

• HIV controllers had a trend toward higher median cIMT than untreated HIV noncontrollers

24Hsue P et al. AIDS. 2009;23:1059-1067.

cIMT, carotid intima media thickness (a validated measure of atherosclerosis); IMT, intima media thickness; VL, viral load.

n = 93

n = 33 n = 96

Mea

n IM

T (m

m)

Mea

n Ca

rotid

IMT

(mm

)

2.0

1.0

0.0

2.5

1.5

0.5

1.0

0.0

2.0

1.5

0.5

P <.001

HIV- HIV+ART-

VL <75

HIV+ART-

VL >75

CD4 >500

HIV- HIV+Elite

Controllers

P <.001P =.13

a All study participants with HIV were recruited from the UCSF SCOPE Cohort, which contains a large group of rare individuals who were recruited on the basis of their ability to control HIV replication in the absence of therapy. HIV- participants were selected mainly from those answering advertisements to participate in research studies who were similar in age and sex to participants with HIV.

• Prospective observational cohort study of patients with HIV• Analysis included patients receiving care from 2002-2009; N=2005 (148 incident CV

events)• Median age: 42 years

• Categorized patients according to the NCEP 10-year CVR score criteria (10-yr CVR)• Analyzed incidence and rates of CVD during observation period and calculated the

relative attributable risks of various traditional and HIV risk factors to incident CVD

25

CV, cardiovascular; CVR, cardiovascular risk; HDL-C, high-density lipoprotein-cholesterol; HTN, hypertension; NCEP, National Cholesterol Education Program.

Lichtenstein KA et al. Clin Infect Dis. 2010;51:435-447.

Attrib

utab

le R

isk,

%

Relative Contribution of Risk Factors to Incident CVD

D:A:D Study Group. N Engl J Med. 2007;356:1723-1735.

0 <1 1-2 2-3 3-4 4-5 5-6 6-7 >7

Inci

denc

e pe

r 100

0 Pe

rson

-Yea

rs

0

1098765

321

4

Total

Number of events: 16 17 20 41 61 62 51 47 30 345

Number of person-years:

11,815

7105902

712,098 14,892

14,394

11,351793

55853 94,469

MI, myocardial infarction.

26

Exposure (years)

MI Incidence

Metabolic Syndrome

• Hypertension• Hypergylcemia• Central obesity• Hypercholesterolemia

28

BP, blood pressure; MS, metabolic syndrome; WC, waist circumference.

Bonfanti PB et al. J Acquir Immune Defic Syndr. 2007;45:426-431.

Prevalence of MS Components in HIV+ Patients and HIV- Controls

P <.0001

P <.0001P <.0001

P <.0001NSSu

bjec

ts, %

• Patients with fat redistribution had significantly increased 10-year CHD risk compared with matched controls

• Patients without fat redistribution did not have increased 10-year CHD risk compared with matched controls

7.4

3.3

P =.002

P =.27

10-y

ear C

HD

-ris

k Es

timat

e (%

)

0

6

7

8

9

10 FraminghamOffspring Study controls

HIV+ patientswith fat redistribution

4.1

5.3

1

2

3

4

5HIV+ patientswithout fat redistribution

Patient Population

(n = 91) (n = 90) (n = 30)(n = 273)

Adapted from Hadigan C et al. Clin Infect Dis. 2003;36:909-916.29

a Study included 91 consecutive HIV+ subjects (65 men and 26 women) who reported recent changes in body fat distribution who were prospectively evaluated from December 1998 through November 1999 at the Clinical Research Center of the Massachusetts Institute of Technology.

• Lipodystrophy (fat redistribution) reported in large numbers of patients with HIV1

• Proportion of affected patients is greater in those receiving certain ARVs

• Prevalence rates of lipodystrophy vary between 11% and 83% in cross-sectional studies

• Lipodystrophy may be a clinical symptom of insulin resistance, diabetes, and increased CV risk1

• Lipodystrophy may be associated with decreased quality of life and poorer ART adherence in affected patients2

30

1 Khunnawat C et al. Am J Cardiol. 2008;102:635-642. 2 Nachega JB et al. Curr HIV/AIDS Rep. 2009;6:121-129.

Lichenstein et al. CID 2010; 51(4):435-447• Looked at MI, non-embolic or hemorrhagic stroke, CAD, angina and

peripheral arterial disease• Assessed the association of latest CD4 count and the CV event• CD4 <350 had a hazard ratio of 1.58• Traditional CV risk factors and a CD4 count <500 were associated

with a greater risk than any cumulative risk of any ARV class or individual drug

Remaining Questions:

• Is there truly a risk of increased incidence of MI in HIV infection that can be separated from background demographics?

• If there is an increased risk, what is it about HIV or immune dysfunction that drives the risk?

• Do potential ART related toxicities influence the incidence of MI?

Freiberg,MS et al JAMA Intern Med March 2013

• Looked at MI only in men 2003 to 2009• 82,459 participants with 33.2% being HIV positive• They were matched not only by traditional risk

factors but by similar demographic and geographic backgrounds

• They determined that the HIV population carried about a 50% increase in risk for MI and that the Framingham risk assessment was likely to underestimate the true risk in the HIV population

Observed rates

Best estimate of predicted rate

0

1

2

3

4

5

6

7

8

No <1 year

1-2 years

2-3 years

3-4 years

4+ years

Duration of ART

Rate

s Pe

r 100

0 Pe

rson

-yea

rs

Schambelan M et al. Circulation. 2008;1182:e48-e53.34

• All patients should be assessed for CVD risk• Those with 2 risk factors should be further evaluated and managed

according to the HIVMA and NCEP guidelines • All patients should be encouraged to stop smoking regardless of CVD

risk, and HTN and diabetes mellitus should be managed as appropriate

• A fasting glucose level and a fasting lipid profile should be obtained from all patients upon initiation of care and every 6-12 months thereafter

• Consider testing 1-3 months after starting or modifying ART • Hemoglobin A1c level should be obtained every 6 months in patients

with diabetes mellitus

35

HIVMA, HIV Medicine Association; IDSA, Infectious Disease Society of America.

Aberg JA et al. Clin Infect Dis. 2009;49:651-681.

Why Is There an Increased Risk for Myocardial Infarction?• Is it the dyslipidemia mainly characterized by a low

HDL and increased triglyceridemia?• Is it the chronic inflammation associated with years of

viral replication before the disease is treated?• Is it due to an altered immune response that persists

despite viral control?• Do our current anti-retroviral medications contribute

in ways we have not yet appreciated?• Do the interventions we employ to decrease risk in HIV

negative people work in HIV infected people?• What about women?

• IRR (95% CI) vs never smoked:• MI: 3.73 (2.46, 5.64); CHD: 2.93 (2.07, 4.14); CVD: 2.32 (1.69, 3.18) within the first year of

smoking cessation• MI: 2.07 (1.19, 3.63); CHD: 1.83 (1.16, 2.89); CVD: 1.49 (0.99, 2.24) after >3 years of smoking

cessation

37

IRR of MI and Smoking Status

IRR of CVD and Smoking Status

IRR, incident rate ratio.

Petoumenos K et al. HIV Med. 2011;12:412-421.

0.5

2.5

5

IRR

0.5

2.5

5

IRR

Never smokedPrevious smokerCurrent smoker

<1 year1-2 years

2-3 years>3 years

Stopped smoking during follow-up:

38Silverberg M et al. Ann Intern Med. 2009;150:301-313.

Results are based on linear regression with adjustment for age, sex, year, lipid-lowering therapy class, months of follow-up, baseline LDL cholesterol and TG levels, number of coronary disease risk factors, past coronary disease or diabetes diagnoses, and hepatitis B or C infection. Model for any statin use is also adjusted for dose-equivalents of different individual statins and concomitant use of other lipid-lowering therapy classes.

Adjusted Percentage Changes in LDL-C and TG Levels Within 12 Months of Lipid-lowering Therapy

Chan

ge in

LD

L-C

Leve

l, %

Chan

ge in

TG

Lev

el, %

HIV-infected patients (n = 616)HIV-uninfected patients (n = 5451)

HIV-infected patients (n = 213)HIV-uninfected patients (n = 1490)

-10

-30

0

-20

-40

-10

-30

0

-20

-40

-50

-60

-70

Any Lipid-lowering Therapy

Any Lipid-lowering TherapyAny Statin

-25.6(P = .001)

-28.3(reference)

-19.9(reference)-19.2

(P = .38)

HIV+ HIV+ HIV+ HIV-HIV- HIV-

-52.1(reference)

-41.2(P <.001)

LDL-C, low-density lipoprotein cholesterol.

a A retrospective cohort study to compare the effectiveness and safety of lipid-lowering therapy in patients with and without HIV infection in an integrated health care delivery system (1996-2005). N = 829 HIV+ patients and 6941 HIV- patients HIV infection beginning lipid-lowering therapy for elevated LDL-C or TG levels.

• HIV infection itself affects endothelial function

• Baseline FMD: 3.68%

• FMD improved during ART:• At Week 4: +0.74% (P ≤.01)• At Week 24: +1.48 (P <.001)• No significant differences between

treatment arms

• No consistent significant correlations between changes in FMD and changes in any lipids or glycemic parameter

• Improvement in FMD significantly correlated with decrease in HIV-1 RNA at Week 24

• No relationship with baseline VL

39Torriani F et al. J Am Coll Cardiol. 2008;12;52:569-576.

-5

-0

5

10

Chan

ge in

FM

D fr

om B

asel

ine

to W

eek

24, %

All Subjects PI-sparing

NNRTI-sparing

NRTI-sparing

FMD, brachial-artery flow-mediated dilation; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

a The ACTG (AIDS Clinical Trials Group) study 5152s is a substudy of ACTG 5142, a prospective, multicenter, randomized, clinical trial that investigated time to virologic failure in ART naive subjects randomly assigned to receive 1 of 3 ART sparing regimens (N = 82).‐ ‐

40Currier J et al. Circulation. 2008;118:e29-e35.

Increasing CV Risk Decreasing CV Risk•Dyslipidemia, insulin resistance, body habitus changes associated with HIV itself and certain components of ART

•Control of viral replication with ART improves endothelial function

•High rates of other CV risk factors, in particular smoking

•Current ARV regimens have more favorable effects on metabolic parameters and morphological changes than earlier regimens

•Prolongation of survival: older patients are intrinsically at greater CV risk

•ART reduces inflammatory markers and immune activation

•HIV providers more aggressive about modification of ART or initiation of lipid-lowering therapies

41

HBV, hepatitis B virus; HCV, hepatitis C virus; CMV, cytomegalovirus.

Deeks SG. Topics HIV Med. 2009;17:118-123.

Suboptimal CD4 gains

Residual inflammation Hypercoagulation

Non-AIDS—related events and premature mortality

Outcome Measures

Age >70 years,HIV-

HIV+, Untreate

d

Long-term (5-10 years)

Treated HIV+Low CD4/CD8 ratio Yes Yes Unknown

Low naïve/memory ratio Yes Yes Possible

Low T-cell proliferative potential

Yes YesPossible

(low CD4 nadir)

Expanded CMV-specific CD8 cells

Yes Yes Yes

Expanded CD28-CD8+ T cells

Yes Yes Unknown

Expanded CD57+ T cells Yes Yes Unknown

Reduced T-cell repertoire Yes Yes Possible

Deeks SG. Annu Rev Med. 2011;62:141-155. 42

43

Outcome Measures

Age >70 years,HIV-

HIV+, Untreate

d

Long-term (5-10 years)

Treated HIV+Increased IL-6 Yes Yes Possible

Increased T-cell activation

Unclear Yes Possible

Reduced thymus function

Yes Yes Unknown

Low IL-2, high IFN-γ (CD8+ T cells)

Yes Yes Unknown

Reduced response to vaccines

Yes YesPossible (CD4

nadir)

Reduced T-cell telomere lengths

Yes Yes (CD8) Controversial

Deeks SG. Annu Rev Med. 2011;62:141-155.

44

Untreated HIV Infection

CMV replication

HIV replication

Loss of immuno-regulatory cells

Thymic dysfunction and loss of regenerative

potential

Loss of gut mucosal integrity and microbial

translocation

Decreased but persistent (1) defects in T-cell regenerative potential; (2) loss of immunoregulatory function; (3) CMV

and other co-pathogen levels; (4) and microbial translocation

Chronic inflammation

T-cell maturation T-cell dysfunctionProgenitor-cell exhaustion

Immunosenescence and clinical disease

Deeks SG. Annu Rev Med. 2011;62:141-155.

• CV risk factors, including metabolic disorders, and CVD are highly prevalent in patients with HIV

• Etiology of CVD and metabolic complications is multifactorial

• Traditional risk factors• HIV infection• ART

• Clinicians caring for patients with HIV should be cognizant of the increased risk of CVD and metabolic disorders in this patient population and manage them appropriately

45

• The number of HIV-infected persons 50 years and older is increasing

• Morbidity associated with normal aging may be enhanced by HIV infection and/or ART

• Clinicians should be aware of the challenges associated with management of an older patient with HIV

• Older patients may present with more advanced HIV disease• Immunologic response in aging patients is less robust than in

younger patients

• Primary health care considerations in patients with HIV should include screening and management of age-related comorbidities

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