Aging and HIVAging and HIV

Steven C. Zell, M.D.Steven C. Zell, M.D.Professor of MedicineProfessor of Medicine

AAHIVSAAHIVSNevada AIDS Education and Training CenterNevada AIDS Education and Training Center

University of Nevada School of MedicineUniversity of Nevada School of Medicine

Survival Trends in HIV-infected Patients Have

Changed Since the Adoption of HAART

Lohse N, et al. Ann Int Med. 2007;146(2): 87-95. Figure 1. Used with permission.

Cumulative survival curve for HIV-infected persons (without hepatitis C coinfection) and persons from the general population. N=383,862 (HIV-infected patients, n=3990; General population controls, n=379,872)

Survival From Age 25 Years

1

0.75

0.5

0.25

0

25 30 35 40 45 50 55 60 65 70

Age (years)

Pro

ba

bil

ity

of

Su

rviv

al

Population

Controls

Late HAART (2000-2005)

Early HAART (1997-1999)

Pre-HAART (1995-1996)

IRS Table IRS Table ((Single Life ExpectancySingle Life Expectancy))

Current Age Expected Longevity Current Age Expected Longevity

25 58.225 58.2

30 53.330 53.3

35 48.535 48.5

40 43.640 43.6

45 38.845 38.8

Impact of HAART on SurvivalImpact of HAART on Survival HIV Prevalence Age HIV Prevalence Age

27% of people living with AIDS in the US are 27% of people living with AIDS in the US are older than 50!older than 50!

Numbers of such persons expected to increase Numbers of such persons expected to increase with increasing survival under HAART treatmentwith increasing survival under HAART treatment

Disproportionate demand on total HIV careDisproportionate demand on total HIV care

Co-morbidities w ageCo-morbidities w age

CVD / PVD / CKD / Htn / DM / Cognitive / CACVD / PVD / CKD / Htn / DM / Cognitive / CA

Screening for non-HIV illnessScreening for non-HIV illness

Lipids / cancer / bone disease, etc.Lipids / cancer / bone disease, etc.

15

The Age of the HIV-Infected Population in the United States* Is Increasing

0

20

40

60

80

100

120

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 ≥65

2004 2007

Estimated Number of Individuals Living With HIV/AIDS in the United States* ≥20 Years of Age (CDC Surveillance Data)1

The age of the HIV-infectedpopulation in the United States is increasing due to2:

• The impact of HIV therapy

• New HIV infections in older patients

*Based on 34 states with confidential name-based HIV-infection reporting.

Age in Years

HIV

/AID

S C

ases

(x

100

0)

1. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 2007;19:12,21. http://www.cdc.gov/hiv/topics/surveillance/resources/reports/. Accessed October 14, 2009.

2. Gebo KA and Justice A. Curr Infect Dis Rep. 2009;11:246-254.

Are Our HIV Clients Older People?Are Our HIV Clients Older People?

Epidemiologic data suggests shortened life-span Epidemiologic data suggests shortened life-span despite HAART?despite HAART?

HAART may produce chronic adverse effectsHAART may produce chronic adverse effects CAD risk increasedCAD risk increased Metabolic abnormalities more commonMetabolic abnormalities more common

Type DM / Htn / Obesity / DyslipidemiaType DM / Htn / Obesity / Dyslipidemia

HAART may not protect from CANCER w AGEHAART may not protect from CANCER w AGE Esophageal / Lung / Rectal (HPV) / Renal / LiverEsophageal / Lung / Rectal (HPV) / Renal / Liver

Conditions seen at earlier age / unusual groupsConditions seen at earlier age / unusual groups Osteopenia / hypogonadism / neurocognitiveOsteopenia / hypogonadism / neurocognitive

In treated patients who achieve durable suppression of the HIV virus, natural ageing, drug specific toxicity, lifestyle factors, persistent inflammation, and perhaps residual immunodeficiency are causally associated with premature development of many

complications normally associated with ageing, including cardiovascular disease, cancer, and osteoporosis or osteopenia.

Deeks S G , Phillips A N BMJ 2009;338:bmj.a3172

©2009 by British Medical Journal Publishing Group

21

Non-HIV Medical Conditions in Older HIV-Infected Patients

The following are non–HIV medical conditions that are important

Bone healthBone health• Non-AIDS malignanciesNon-AIDS malignancies• Cardiovascular disease riskCardiovascular disease risk• Metabolic disorders: Type II DM / DLDMetabolic disorders: Type II DM / DLD• Hypertension • Chronic Kidney disease• Cognitive function / dementia• Depression / Mental health• Frailty• Sexually transmitted diseases• Tobacco Addiction• Substance use

Henry K. Curr HIV/AIDS Rep. 2009;6:153-161.

When to initiate ARV Tx in Advancing Age?When to initiate ARV Tx in Advancing Age?

Traditional arguments against starting therapyTraditional arguments against starting therapy Life-long cumulative drug toxicityLife-long cumulative drug toxicity Non-adherence leading to resistanceNon-adherence leading to resistance Ability to “resuscitate” even the most advancedAbility to “resuscitate” even the most advanced

Thymus involutes w age-makes “naïve T cells”Thymus involutes w age-makes “naïve T cells” Lower CD4 nadir= more complicationsLower CD4 nadir= more complications

CVD eventsCVD events

Non-AIDS malignanciesNon-AIDS malignancies

Neuro-cognitive dysfunctionNeuro-cognitive dysfunction

WHY WAIT TO TREAT?WHY WAIT TO TREAT?

Limitations of Screening for CVD in HIVLimitations of Screening for CVD in HIV

Framingham risk under-estimates noted CVD eventsFramingham risk under-estimates noted CVD events

Symptomatic CVD requires >70% stenosisSymptomatic CVD requires >70% stenosis Most fatal plaque rupture w lesions < 50% stenosedMost fatal plaque rupture w lesions < 50% stenosed

Reliance on acceptable LDL-C levels dangerousReliance on acceptable LDL-C levels dangerous Atherogenic non-HDL-C: ACCORD StudyAtherogenic non-HDL-C: ACCORD Study HIV patients have very low HDL-CHIV patients have very low HDL-C

HIV patients are “fatty” for years before therapyHIV patients are “fatty” for years before therapy TNF-alpha promotes lipolysisTNF-alpha promotes lipolysis High levels of CRPHigh levels of CRP Lipoatrophy: peripheral fat loss and visceral fat gainLipoatrophy: peripheral fat loss and visceral fat gain FFA accumulation leads to IRFFA accumulation leads to IR

Surrogate marker Trigs / HDL-C> 3.5Surrogate marker Trigs / HDL-C> 3.5

Exposure to HAART is Associated with Increased Risk of Myocardial Infarction (MI) Over Time

DAD Study Group. N Eng J Med. 2007;365:1723-1735. © 2007. Massachusetts Medical Society. All rights reserved. Used with permission.

Total

No. of Events 16 17 20 41 61 62 51 47 30 345

No. of Person-Yr 11,815 7,105 9,027 12,098 14,892 14,394 11,351 7,935 5,853 94,469

Exposure (yr)

Inc

ide

nc

e p

er

1,0

00

Pe

rso

n-Y

r10

9

8

7

6

5

4

3

2

1

00 <1 1-2 2-3 3-4 4-5 5-6 6-7 >7

26Wand H, et al. AIDS. 2007;21:2445-2453.

Metabolic syndromea in HIV-infected patients within 3 years of initiation of HAART

a Percentage of patients with metabolic syndrome defined by ATP III criteria (data from metabolic syndrome defined by International Diabetes Federation not shown)

b Median follow-up 192 weeks

Metabolic Syndrome (MS) Prevalence in HIV-infected Patients Initiated on HAART

N=881

Per

cen

tag

e o

f P

atie

nts

(95%

co

nfi

den

ce in

terv

al)

0

10

20

30

40

50

60

70

80

90

100

8.5

26.6

Patients Developing MS During Follow-upb

Treatment-naïve Patients with MS at Baseline

27

Higher Proportions of CV Risk Factors in HIV-infected Individuals vs Non-infected Controls

CV Risk Factors in HIV vs Non-HIV Cohorts

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

Per

cen

tag

e o

f P

atie

nts

21.2%

15.9%

11.5%

6.6%

23.3%

17.6%

*

*

*

* HIV vs Non-HIV, P<0.0001

0

5

10

15

20

25

30

35

40

45

50

Hypertension Diabetes Dyslipidemia

HIV (n=3851)

Non-HIV (n=1,044,589)

I If 2 or more are present perform a 10 year cardiovascular risk assessment

NCEP ATP-III GuidelinesWhere is HIV as a Risk Factor?

31

Rates of Non-AIDS-defining Malignancies in HIV-infected vs Non-HIV-infected Persons

Patel P, et al. Ann Intern Med. 2008;148:728-736.

ASD and HOPS (HIV-infected Population, N=61,728)

SEER (General Population, N=334,802,121)

Sta

nd

ard

ized

Inci

den

ce R

ates

p

er 1

00,0

00 P

erso

n-y

ears

Anal

Hodgk

in

Lym

phom

a

Live

r

Lung

Mel

anom

aO

roph

aryn

geal

Color

ecta

l

Breas

t

Prost

ate

78.2

64.4

35.4

84.9

37.5 36.9

66.2

96

37.5

1.3 3.6 4.7

23.4

9.9 11.7

21.1

82.7

60.9

0

10

20

30

40

50

60

70

80

90

100

ASD=Adult and Adolescent Spectrum of HIV Disease; HOPS=HIV Outpatient StudySEER=Surveillance, Epidemiology, and End Results

SCREENING FOR ANOGENITAL HUMAN PAPILLOMAVIRUS (HPV)

Recommendation44. HIV-infected men and women with HPV infection are at increased risk for anal dysplasia and cancer. MSM, women with a history of abnormal cervical Pap test results, and all HIV-infected persons with genital warts should be considered for anogenital HPV screening and anal Pap tests (C-III).

Key Facts:HIV-pos. MSM have 40 fold increase in anal CAHAART has not decreased anogenital CA incidenceIncreased diagnosis “true effect vs. surveillance bias vs. longevity”Anal HPV present in 95% MSMLikely lifetime persistence risk increases w ageSensitivity good for anal PAP / specifcity poorAnoscopy required for ASCUS or worseDifficult to implement due to costs / referral limitations

IDSA Comments of Anogenital Cancer Screening

DEXA Scanning and HIVDEXA Scanning and HIV

No randomized data to suggest will No randomized data to suggest will fracture risk fracture risk

Case by case DEXA screeningCase by case DEXA screening Postmenopausal femalesPostmenopausal females Hypogonadal malesHypogonadal males ““Frail” patients prone to fallsFrail” patients prone to falls

Neurocognitive diseaseNeurocognitive disease PML / PARKINSON’SPML / PARKINSON’S

Neuromuscular Neuromuscular ASEPTIC NECROSIS OF THE HIPASEPTIC NECROSIS OF THE HIP

Chronic steroid therapy / PPI use?Chronic steroid therapy / PPI use? Chronic alcohol usageChronic alcohol usage Thyroid replacementThyroid replacement

Vitamin D DeficiencyVitamin D Deficiency

Worldwide deficiency as declared by LabCorpWorldwide deficiency as declared by LabCorp

Dietary Ca intake declines w ageDietary Ca intake declines w age Near 700 mgs dailyNear 700 mgs daily Need 1200-1500 mg to maintain bone mass >55Need 1200-1500 mg to maintain bone mass >55

25-OH Vitamin D is recommended measurement25-OH Vitamin D is recommended measurement > 32 ng /ml for optimum Ca absorption> 32 ng /ml for optimum Ca absorption > 40 ng /ml for “immune health” and CVD risk reduction> 40 ng /ml for “immune health” and CVD risk reduction

Daily amount 800-2000 IU w poor diet intake CaDaily amount 800-2000 IU w poor diet intake Ca

Vit D2 50,000 u/ cap- significant deficiencyVit D2 50,000 u/ cap- significant deficiency One per week x 3 months / bi-monthly x 3 moreOne per week x 3 months / bi-monthly x 3 more

Unique Factors Hindering HIV Care: Aged Unique Factors Hindering HIV Care: Aged

Older people living with HIV face a double stigmaOlder people living with HIV face a double stigma AgeAge HIVHIV

Difficult for seniors, women in particular, to disclose to Difficult for seniors, women in particular, to disclose to family, friends, community HIV statusfamily, friends, community HIV status

Smaller network of aged HIV friends for supportSmaller network of aged HIV friends for support

Cross-over symptoms between HIV and agingCross-over symptoms between HIV and aging Fatigue, wt loss, dementia, skin conditionsFatigue, wt loss, dementia, skin conditions

Misdiagnosis of OIs more frequent / delayedMisdiagnosis of OIs more frequent / delayed

Social isolation leads to depressionSocial isolation leads to depression Not a clear cut diagnosis in elderly personsNot a clear cut diagnosis in elderly persons Losing interest is common with agingLosing interest is common with aging

Training and Future HIV CaregiversTraining and Future HIV Caregivers

HIV physicians prefer focused medical practicesHIV physicians prefer focused medical practices Non-HIV issues became burdensomeNon-HIV issues became burdensome

As medical conditions in the HIV elderly dominate who will As medical conditions in the HIV elderly dominate who will manage the care?manage the care?

Superdocs expert in HIV and geriatricsSuperdocs expert in HIV and geriatrics Fragmentation of tertiary careFragmentation of tertiary care

Neurology / dermatology / cardiology / ortho / urologyNeurology / dermatology / cardiology / ortho / urology

Likelihood multiple clinicians involved with aging HIV population Likelihood multiple clinicians involved with aging HIV population Difficulty with coordination of care / sharing informationDifficulty with coordination of care / sharing information Drug treatments and need for supervision by single personDrug treatments and need for supervision by single person

Drug-drug interactions / contraindications / adverse eventsDrug-drug interactions / contraindications / adverse events

Summary ConclusionsSummary Conclusions

HIV population is aging due to treatment effectHIV population is aging due to treatment effect

HIV despite effective therapy has limits on longevity as “HIV HIV despite effective therapy has limits on longevity as “HIV effect” ages persons more quicklyeffect” ages persons more quickly

As HIV clinics age, less time will be given to the young and As HIV clinics age, less time will be given to the young and more spent on the aged and co-morbiditiesmore spent on the aged and co-morbidities

Economic challenges exist to provide primary care to an aging Economic challenges exist to provide primary care to an aging HIV populationHIV population

Training and education needs to focus on co-morbid HIV Training and education needs to focus on co-morbid HIV related conditions seen with agingrelated conditions seen with aging

A fragmented model of “multi-docs” providing specialized care A fragmented model of “multi-docs” providing specialized care for older HIV persons may be too cumbersome to workfor older HIV persons may be too cumbersome to work