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Aging with HIV infection

Bill Powderly MDSchool of Medicine and Medical SciencesUniversity College DublinIreland

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Overview

• As patients get older, common diseases become more prevalent.  – Relevant impact of varying risk factors is difficult to

determine and varies among co-morbidities.– Relationship with HIV or antiretroviral therapy is also

variable and of different importance.

• Specific examples: cardiovascular disease, bone disease

• Implications for management• Implications for future research.

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Ageing of HIV population Swiss Cohort

Hasse et al, CROI 2011, O-161

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Incidence of Multiple Comorbidities Increases With Age in HIV-Infected

Pts

Guaraldi G, et al. Glasgow 2008. Abstract P300.

No comorbidity1 comorbidity2 comorbidities3 comorbidities4 comorbidities5 comorbidities

0

25

50

75

100

≤ 30 31-40 41-50 51-60 > 60Age (Years)

Pat

ien

ts (

%)

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Ageing

Antiviral treatment

HIV infection

Interplay of time with morbidity

• Risk of “co-morbidities” increases as individuals get older

• HIV does not cause these illnesses

• However HIV and/or ART may increase the risk

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HIV Associated Non AIDS Conditions

• Usual risk factors determine most of the risk– Increasing age and substance use add to risk

• Additonal risk may be due to HIV, to ART or both– May/may not be associated with CD4 or HIV-1 RNA– role of Chronic viral infection

– role of Chronic inflammation

• Major Issue for HIV researchers:– how important is the additional risk– Are the effects of HIV reversible or preventable

• Major issue for HIV providers and patients– Is management different

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Deeks, Annu. Rev. Med. 2011. 62:141–55

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Life expectancy at birth (men)

Glasgow (deprived area) 54

Australian Indigenous 59

India 61

Philippines 65

Lithuania 66

US 75

UK 76

Australian average 77

Glasgow (affluent area) 82

World Health Report 2006, Hanlon et al 2006, AIHW 2008

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HIV Infection is an independent risk factor for atherosclerosis

*p<0.01, **p<0.001, ***p<0.0001; †There was a significant gender interaction

Grünfeld C et al. AIDS 2009

Estimated effect (mm)

Characteristic Internal carotid Common carotid

HIV infection 0.15** 0.033*

Male† 0.13*** 0.054***

Current smoker 0.17*** 0.020**

Past smoker 0.09*** 0.020***

Diabetes 0.12*** 0.026***

Age (per 10 years) 0.16*** 0.073***

Systolic BP (per 10 mmHg) 0.05*** 0.025***

Diastolic BP (per 10 mmHg) -0.07*** -0.026***

Total cholesterol (per 10 mg/dL) 0.009*** 0.004***

HDL (per 10 mg/dL) -0.020*** -0.011***

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HIV and Heart disease

• Multiple studies show increased risk of MI and other ischemic CV events in HIV infected patients– Risk related to chronic inflammation– Risk related to ART – espec specific PIs and

NRTIs• However, most clinical events are seen in

patients with other ‘standard’ risk factors– Emphasizes need for routine primary and

secondary prevention

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BMD Changes in normal populationC

han

ge

in B

on

e V

olu

me

(%)

Women

Men

Peak

Relative influence on peak bone mass (men):40% to 83% genetic 27% to 60% environmental 0.5%-1.0% reduction in

bone volume/year

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

0

0.2

0.4

0.6

0.8

1.0

0 30 60 8010 4020 50 70

0.1

0.3

0.5

0.7

0.9

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Bone mineral loss and HIV

• Multiple cohort studies show increased prevalence of bone demineralization (osteopenia and osteoporosis) in HIV+ patients as compared to controls

• Seen in untreated and treated patients– HIV effect - virus or disease– Treatment effect – particularly with initiation

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SecondaryClassic

Risk Factors for Decreased BMD in HIV-infected Individuals

Diagram adapted from Glesby MJ. Clin Infect Dis 2003; 37(Suppl 2):S91–S95

Female sex Decreased physical activity

Decreased bone acquisition

Smoking

White race

Family history

Alcohol

Increasing age

Amenorrhoea /premature menopause

Hypogonadism

Malnutrition/low BMI

Renal dysfunction

Medications (e.g. corticosteroids, anticonvulsants, anticoagulants)

Chronic diseases (e.g. hyperthyroidism, hyperparathyroidism, liver disease, rheumatological conditions, eating disorders, etc.)

Bone Mineral Density

HIV / HAART-related

Cytokines (eg TNFa, IL6)

Nucleoside analogues /mitochondrial dysfunction

Protease inhibitors

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Potential effects of HIVC

han

ge

in B

on

e V

olu

me

(%)

Women

Men

Peak

Decreased total bone mass

Increased rate of bone demineralization

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

0

0.2

0.4

0.6

0.8

1.0

0 30 60 8010 4020 50 70

0.1

0.3

0.5

0.7

0.9

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Fracture Prevalence in HIV-infected and non-HIV-infected Persons

Triant, JCEM, 2008

MGH/Partners Healthcare System: 1996-2008

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Other co-morbidities of Age

• Cancer– Cancer increasingly prevalent– Unclear if risk is truly increased

• Renal Disease– Renal function slowly declines with age (espec > 70)– Certain HIV drugs can affect CrCl – Long-term effect on renal function unknown

• Neurocognitive decline– As yet, no evidence of significant increased prevalence

or earlier incidence

• Frailty

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Frailty in HIV

• HIV associated with a >10-year earlier occurrence of a phenotype similar to frailty (MACS)– Risk increased with decreasing CD4 cell count, – Older age, lower educational level, and clinical AIDS

were independently associated with frailty phenotype

• Time with frailty phenotype independently associated with risk of AIDS or death, even after HIV suppression.

Desquilbet L et al, J. Gerontol A Biol. Sci. Med. Sci. 62:1279-1286, 2007.Desquilbet L et al, J. Acquir. Immune Def. Syndr. 50:299-306, 2009.

Onen N et al. J Infect. 59:346-52, 2009.

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As patients get older, common diseases become more prevalent.

Sorting the relevant impact of varying risk factors is difficultCommon tendency to ascribe an apparent increase to HIV or

therapy is probably incorrect

HIV Infection and or HAART

Non-HIV related risk

factors

Genetic

InfluencesAGE

Co-morbidity

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Management issues in older HIV+ve patient

• Need for regular screening and health maintenance

– Fasting lipids and glucose, renal function, bone disease– Cancer screening as would be performed in general population– www.europeanaidsclinicalsociety.org

• Antiretroviral therapy

– ?Earlier initiation– Choice of therapy to avoid metabolic and other toxicities

• Management of Complications and co-morbidities

– Prevention if possible– Manage other reversible factors -smoking– Polypharmacy - Awareness of drug-drug interactions

– Recognition that HIV+ve patients may not respond as well • E.g. lipid-lowering therapy

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www.europeanaidsclinicalsociety.org

Prevention and Management

of Non-Infectious Co-Morbidities in HIV