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. –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.

Ageing of HIV population Swiss Cohort Hasse et al, CROI 2011, O-161

Incidence of Multiple Comorbidities Increases With Age in HIV-Infected Pts Guaraldi G, et al. Glasgow Abstract P300. No comorbidity 1 comorbidity 2 comorbidities 3 comorbidities 4 comorbidities 5 comorbidities ≤ > 60 Age (Years) Patients (%)

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

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

Deeks, Annu. Rev. Med :141–55

Life expectancy at birth (men) Glasgow (deprived area)54 Australian Indigenous59 India61 Philippines65 Lithuania66 US75 UK76 Australian average77 Glasgow (affluent area)82 World Health Report 2006, Hanlon et al 2006, AIHW 2008

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) CharacteristicInternal carotidCommon carotid HIV infection0.15**0.033* Male † 0.13***0.054*** Current smoker0.17***0.020** Past smoker0.09***0.020*** Diabetes0.12***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***

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

BMD Changes in normal population Change in Bone Volume (%) 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:

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

Secondary Classic 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 TNF , IL6) Nucleoside analogues /mitochondrial dysfunction Protease inhibitors

Potential effects of HIV Change in Bone Volume (%) Women Men Peak Decreased total bone mass Increased rate of bone demineralization Age (Years) Orwoll ES, et al. Endocr Rev. 1995;16:

Fracture Prevalence in HIV-infected and non-HIV-infected Persons Triant, JCEM, 2008 MGH/Partners Healthcare System:

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

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: , Desquilbet L et al, J. Acquir. Immune Def. Syndr. 50: , Onen N et al. J Infect. 59:346-52, 2009.

As patients get older, common diseases become more prevalent. Sorting the relevant impact of varying risk factors is difficult Common tendency to ascribe an apparent increase to HIV or therapy is probably incorrect HIV Infection and or HAART Non-HIV related risk factors Genetic Influences AGE Co-morbidity

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 – 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

Prevention and Management of Non-Infectious Co-Morbidities in HIV