hiv and aging kathleen k casey, md director, aids ambulatory care center jersey shore university...
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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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