Aging with HIV infection
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www.ias2011.org Aging with HIV infection Bill Powderly MD School of Medicine and Medical Sciences University College Dublin Ireland
description
Aging with HIV infection. Bill Powderly MD School of Medicine and Medical Sciences University College Dublin Ireland. 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. - PowerPoint PPT Presentation
Transcript of Aging with HIV infection
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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)
Patie
nts
(%)
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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) 54Australian Indigenous 59India 61Philippines 65Lithuania 66US 75UK 76Australian average 77Glasgow (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 carotidHIV 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
hang
e in
Bon
e Vo
lum
e (%
)
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 activityDecreased bone acquisition
Smoking
White race
Family history
AlcoholIncreasing age
Amenorrhoea /premature menopause
Hypogonadism
Malnutrition/low BMIRenal 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
hang
e in
Bon
e Vo
lum
e (%
)
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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Prevention and Managementof Non-Infectious Co-Morbidities in HIV
