Aging Gracefully with HIV

Jonathan S. Appelbaum, MD, FACP, AAHIVS

Disclosure of Financial RelationshipsThis speaker has the following financial relationships with commercial entities to

disclose:• Salary/Contractual Services: Merck – Terminated

This speaker will not discuss any off-label use or investigational product during the program.

This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.

Objectives

• Implement the newest screening and treatment guidelines for osteoporosis, hyperlipidemia and cancer screening as it pertains to HIV patients

• Identify additional screening needs and proper treatment of HIV patients that are not recommended for the general population

Case 1

• 95 yo AAF previously well presents with FTT and memory problems for the past several years

• PMH: HTN, depression, h/o corneal transplant

• Meds: HCTZ, fluoxetine• Soc: lives with daughter, husband died

1995. No Tobacco, ETOH, IDU

On Exam• Thin woman (BMI 19)• Good skin turgor, no rashes• Edentulous, white plaque on posterior

pharynx• No lymphadenopathy or palpable thyroid• Lungs and cardiac exam WNL• No abdominal masses, stool heme neg• MMSE 24• Neuro exam non-focal

How would you prioritize this work up?

A. CBC/LFT’s/thyroid function tests

B. EGD/Colonoscopy

C. Chest/Abdomen/ Pelvic CT

D. HIV test

E. A first, then D, then B&C if needed

A. B. C. D. E.

0% 0% 0%0%0%

The tests return…..• CMP, TSH normal• Mild normocytic normochromic anemia• EGD, colonoscopy negative• chest/abdomen/pelvic CT normal • HIV Ab+, CD4=141 VL=250K• Other Labs: RPR+ 1:8

CDC Recommendations for HIV Testing

(from MMWR, September 26, 2006, 55(RR 14); 1-17)

Epidemiology

• Increasing Prevalence– Prolonged survival due to HAART– New Infections

Why are older patients getting infected?

Why do you think that the number of older patients with HIV is

increasing?

Why are older patients getting infected?

• Patient lack of awareness of HIV risk factors (sex and drugs)– Many older people are newly single – Belief that HIV only affects younger people

• Unprotected sexual activity– Use of sildenafil and other ED drugs may contribute to

increased rates of sexual activity – Menopause= No risk for pregnancy=No condom– No training in safer sexual activities

• Lack of HIV prevention education targeted at older people

• Seniors not considered at risk: don’t ask, don’t tell

Sex is Not Only for the Young

Lindau NEJM 2007 357(8):762-774

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Median CD4 count and the percentage of patients with a CD4 count ≥350 cells/mm3, at first presentation for HIV

clinical care, by age

<50yo: absolute increase in median CD4 = 67 cells/mm3

≥50yo: absolute increase in median CD4 = 63 cells/mm3

Althoff, AIDS Res Therapy 2010

Prevalence of AIDS, 12 Months after HIV Diagnosis by Age, 2007

HIV surveillance Report, Volume 20, CDC (2010)

Clinical Outcomes in Older Patients Treated with ART

• Virologic Suppression• Immunologic Response• Mortality

Mean Increase in CD4 by Age 2 years after ART

6 months 12 months 18 months 24 months0

50

100

150

200

250 18-<30 years 30-<40 years 40-<50 years 50-<60 years≥60 years

Months since ART initiationAlthoff K AIDS 2010

What are older HIV-infected patients dying from?

A. PCP pneumonia

B. Wasting syndrome

C. Malignancy

D. Dementia

A. B. C. D.

0% 0%0%0%

The Changing Epidemic

ART-CC. CID, 2010.

Among those initiating HAART(1996-2006)

HIV Outcomes with ART: What we Know Already

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 #1-Follow-up

• AZT/3TC/ABC/EFV: – Developed hallucinations

• AZT/3TC/ABC/LPV/r: – Hepatitis

• TDF/FTC/atazanavir: – Renal insufficiency

• ABC/3TC/atazanavir: – Undetectable, CD4 400

Recommendations When to Initiate Therapy

• Antiretroviral therapy should be initiated in all patients older than 50 who have a CD4 count < 500 cells/mm3 .

• Antiretroviral therapy should be initiated in all patients older than 50, regardless of CD4 cell count, with the following conditions: AIDS-defining illness, HIV-associated nephropathy, or chronic hepatitis B virus infection.

• For patients over age 50 who have a CD4 count > 500 cells/mm3, antiretroviral therapy should be considered. Factors favoring initiating therapy include plasma HIV RNA levels greater than 50,000 copies/ml, greater than 100-point decline in CD4 count in prior 12 months, or risk factors for cardiovascular disease.

Normal Aging Process

• Loss of Bone and Muscle Mass

• Weight Loss• Decrease in GFR• Memory Loss• Immunosenescence

Treatment Issues in Older HIV Patients

• Older people may have age-related losses of kidney and/or liver function which may change metabolism of drugs

• Drug-drug interactions• Toxicities significant• Older people often excluded from

many clinical trials and few subgroup analysis in older patients

• Little pharmacokinetic data at extremes of age

Case #2• 63 yo AAF HIV x 10 yrs, CD4 420, VL <50• PMH: HTN, depression, DM, hyperlipidemia• Meds: emtricitabine/tenofovir/efavirenz,

HCTZ, citalopram, glargine insulin, lisinopril, EcASA, pravastatin

• SH: lives alone, No tobacco,, IDU, has boyfriend and uses condoms intermittently

• Difficulty with adherence to non-ART medicines

• HbA1C >10, SBP >160

Number of non-HIV meds by age

B Haase CROI 2011

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Incidence of comorbidities: by age

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Potential Comorbidities Among Older Patients With HIV

• Cardiovascular disease• Metabolic disorders

– Diabetes– Dyslipidemias

• Neurocognitive abnormalities• Liver and renal problems• Bone disorders

– Osteopenia– Osteoporosis

• Malignancies

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

Observed Expected in age adjusted group

P value

NHL 39 43 <.001

Cervical 39 41 .03

Rectal 46 51 .002

Lung 49 53 .001

Hodgkin's 41 38 <.001

Breast 44.5 45 .2

Prostate 59 59 .5

Shiels Annals of Int Med 2011

• For most cancers: there is no difference in age at cancer diagnosis among persons with AIDS compared to the general population.

Case #3• 64 yo WM, HIV+ 22 years, no OIs.• Smokes 1 ppd x 40 yrs• Multiple ART, now on boosted darunavir,

etravirine, raltegravir• CD4 321, HIV RNA <48 c/ml3

• Facial lipoatrophy, truncal lipohypertrophy

• Other meds: metformin, lisinopril, ASA• Reports decreased libido and ED

To evaluate this patient’s concerns, he should have:

A. CBC/LFT’s/thyroid function tests

B. PSA

C. Free Testosterone

D. Total Testosterone

E. All of the above

A. B. C. D. E.

0% 0% 0%0%0%

Endocrine• Testosterone Def: 54% 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 46 (IQR 39-49)

• Associated with increased symptoms of estrogen withdrawal

Klein CID 2005; Schoenbaum E CID 2005

Which of the following recommendations should be your first counseling priority?

A. Diet?

B. Smoking?

C. Exercise?

D. BP control?

E. DM management?

A. B. C. D. E.

0% 0% 0%0%0%

Law et al. HIV Med. 2006;7:218-230.

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rates

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Observed and predicted MI rates according to ART exposure(D:A:D Study n=23,468)

N=5292 N=6805 N=9050 N=10,574 N=8890N=5973

Incidence of MIs is low: 345 over 94,469 patient-years follow-up (3.7/1,000 patient-years)

D:A:D Study: Is the Framingham Risk Estimation Valid in HIV-Infected Patients?

n = ART exposure

D:A:D Study: Risk Factors for CHD in an HIV+ Population

Lundgren J, et al. 12th CROI; 2005; Boston. Abstract 62. Copenhagen HIV Programme (D.A.D)

Relative Rate of Myocardial Infarction (95% CI)Adjusted for BMI, HIV risk, cohort, calendar year and race

Diabetes mellitus (yes versus no)

Hypertension (yes versus no)

Better Worse

0.1 0.5 1 5 10

Family history

Previous CVD

Male gender

Age per 5 years older

Smoking

Drug class: not sufficient # of events to examine yet

cART Therapy RR 1.17 (1.08-1.26)

Case #3—follow-up• Free/total testosterone decreased• PSA, CBC, LFTs normal• Started on testosterone replacement• Appropriate lab follow up done, no

improvement in symptoms• Sildenafil added (dose-adjusted) with

improvement

Recommendations: Lipids• There is insufficient evidence to alter

current recommendations for management of dyslipidemia or CVD/ cerebrovascular disease screening by specific age criteria.

• Use Framingham Risk Score to guide decision.

Case #4

• 77 yo WM HIV x 20 years, CD4 750, VL<50

• PMH: depression, HCV+• Meds: tenofovir/emtricitabine, atazanavir

with ritonavir• SH: lives alone, divorced, MSM, 2

children, 4 grandchildren; no tobacco/ IDU, rare ETOH

Should this patient be screened for osteoporosis?

A. Yes

B. No

C. Don’t Know

A. B. C.

0% 0%0%

BMD Decreases With Age

Orwoll ES et al. Endocr Rev. 1995;16(1):87-116.

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Age (Years)40 50 60 70

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Mean ±SE

MaleFemale

Case #4 (con’t)

• 77 yo WM HIV x 20 years, CD4 750, VL<50

• Meds: tenofovir/emtricitabine, atazanavir plus ritonavir

• SH: lives alone, divorced, MSM, 2 children, 4 grandchildren; no tobacco/ IDU, rare ETOH

• January 2011 Ice storm• Falls and breaks multiple bones

BMD Lower and Fracture prevalence 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

Triant J Clin Endo Metab 2008

Arnsten AIDS 2007

Recommendations: Osteoporosis Screening

• Since older patients have bone loss due to osteoporosis, and since many HIV-infected patients on ART have accelerated bone loss, screening for (and aggressive treatment of) osteoporosis should be done

• Since vitamin D deficiency is prevalent in older HIV-infected persons, screening for vitamin D deficiency is warranted

Frailty• Frailty phenotype: 3 of 5 (weight loss,

exhaustion, weakness, slowness, and low physical activity). – earlier occurrence in HIV-infected patients

• Functional status – may be better indicator

Frailty increases with age and time with HIV

Desquilbet, et al. J Gerontol Med Sci 2007;62A:1279-86

HIV-infected for 8-12 years at age 55 13.4% exhibit the frailty phenotype –

9-fold higher risk than age-matched controls

VACS Risk Index

Points HR

Age <5050-64>65

0927

1.01.452.94

CD4 <5050-99100-199200-349>350

17141180

1.981.721.541.381.00

AIDS def. illness 7 1.31

HIV-1 RNA >5.0 Log 3 1.14

Hemoglobin >1210-12<10

0913

1.001.431.67

FIB-4 <1.451.45-3.24>3.25

01018

1.001.502.09

est GFR<30 12 1.61

ETOH or Drug Use 8 1.35

Hep B or HCV 9 1.45

Justice 2010 HIV Medicine

VACS - Veterans Aging Cohort Study

Survival by VACS Risk Score(6 Years)

Justice 2010 HIV Medicine

Case 5 Presentation

• 77 yo AAF HIV x 5 years, CD4 500, VL<50

• PMH: HTN, arrhythmia with AICD, depression,

• Meds: tenofovir/emtricitabine/efavirenz, carvedilol, HCTZ, citalopram, pravastatin

• SH: Caretaker for grandchildren, husband died 2008, No tobacco, ETOH, IDU

• Family is unaware of diagnosis, impacts adherence to ART

General Routine Health Maintenance

• All Medications• Tobacco/ETOH/drug use• Nutrition• Injury Prevention: Burns/Falls/Driving• Bowel Habits/Incontinence• Psychosocial issues-$, end-of-life,

social support and assisted living/SNF

Recommendations: Cancer Screening• As part of general health maintenance practices,

cancer screening in clinically stable HIV-infected patients 50 years and older should be in accordance to current guidelines for the general population.

• For cervical cancer, anal cancer, and liver cancer where HIV-specific recommendations exist, these guidelines should be adhered to instead.

• For all patients, providers should take into consideration functional status and life expectancy in applying these recommendations.

When to stop screening• When life expectancy less than natural

history of disease: for example, colorectal cancer

• Patient desires/expectations• Current guidelines—for example, ACP

and colon cancer screening after age 75

Other Important Issues• Sexuality• Mobility• Mentation/Depression• Hearing/Vision• Activities of daily living

Conclusions• HIV infection is increasing in the older population• Older patients present later=>need to improve

testing and linkage to care• Compared to younger patients, older HIV patients

have:– Better virologic response, less immunologic boost,

shortened survival

• Psychosocial issues and advanced directives are important

Recommendations• Start older patients with ART earlier for improved CD4 counts and

reducing comorbidities– Watch closely for side effects/toxicities

• Screen for comorbid disease (but stop screening when appropriate!)– DXA for osteoporosis

– Cancer screening

– STD’s

• Avoiding comorbid disease– Vaccinations (Flu, S. pneumoniae)

– Smoking cessation, exercise, diet

– Treat lipids, HTN

• Treat Comorbid disease– SA/MH

– HCV

• Address psychosocial issues and advanced directives

Treatment Recommendations

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