Future challenges for clinical care of an ageing population infected with HIV: a geriatric -HIV modelling study

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Future challenges for clinical care of an ageing population infected with HIV: a geriatric -HIV modelling study Guaraldi G 1, De Francesco D 2, Malagoli A 1, Theou O 3, Zona S 1, Carli F 1, Dolci G 1, Mussini C 1, Kirkland S 4, Mussi C 5, Cesari M 6, Rockwood K 7 1 Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia; 2 HIV Epidemiology and Biostatistics Group (HEBG) at UCL London; 3 Geriatric Medicine Research, Dalhousie University; 4 Department of Community Health & Epidemiology, Dalhousie University; 5 Geriatrics Division, Uni- versity of Modena and Reggio Emilia, Modena, Italy; 6 Geŕontopo le, Centre Hospitalier Universitaire de Toulouse, Toulou- se, France; 7 (1) Geriatric Medicine Research, Dalhousie University; (2) Geriatric Medicine, Institute of Brain & Behavioural Sciences, University of Manchester

The average age HIV-positive patients is constantly increasing; HIV-specialist physician average age is constantly increasing; this is a matter of fact Background 5 years 1 st day of school 25 years MD degree 50 years, NOT YET OLD! A geriatric definition of old-age: 65-75 YRS: Youngest old, 76-84 YRS: Old; >85: Oldest-old

Age distribution of HIV+ patients attending MHMC 2006: Median age 40 yrs 2015: Median age 51yrs Guaraldi G, personal comunication 2016

In the ATHENA cohort, proportion of patients on ART aged 50 years old will increase from 28% to 73% between 2010 and 2030 Smit M, Lancet Infect Dis. 2015 Jul;15(7):810-8.

The burden of NCDs mostly driven by larger increases in cardiovascular disease Smit M, Lancet Infect Dis. 2015 Jul;15(7):810-8.

While people generally accumulate more health problems with age, not everyone of the same age experiences the same health status or risk for adverse outcomes 83 years old; HTN, Hyperlipidemia, prior MI 83 years old; HTN, Hyperlipidemia, prior MI Frailty has been proposed as a measure of biological (opposed to chronological) aging and a measure of overall health status

Objective We aimed to estimate levels of Frailty and its implications for HIV care in Italy up to 2030. Falls and Instrumental Activities of Daily Living (IADL) were used as proxy of geriatric syndromes and disability in the geriatric population

Methods Geriatric age categories were chosen: <35, 35-49, 50-64, 65-75, >75 An individual-based model of the ageing population of the Modena HIV Metabolic Clinic cohort(mhmc) was constructed using data collected between 2009 and 2015 from 2982 patients. The model follows patients enrolled to the clinic up to 2015 and generates new entries on a yearly basis up to 2030. Number, age and gender of new entries were modelled using trends observed in the period 2009-2015. The relationship between age and gender, falls and disability, observed in 2014-2015 at MHMC was postulated to constant over time.

Methods Frailty Index (FI), quantified as the proportion of deficits present out of a total of 37. FI at enrolment was generate from a Gamma distribution with age- and gender-specific parameters estimated using the MHMC 2009-2015 data. We defined Frail a patient with FI between 0.3 and 0.4 and Most-frail a patient with FI>0.4. Changes in the FI over a one-year period and death rates were modelled following a validated mathematical model developed in a large Canadian ageing population with parameters adjusted to best represent the changes observed in the MHMC 2009-2015 population. Geriatric syndromes were evaluated by means of a selfreported fall frequency in the past 12 months and defined as one or more falls (i.e. unexpectedly dropping to the floor or ground from a standing, walking, or bending position). Disability was assessed with IADL: 8 categories of activities of daily function (housekeeping, money management, cooking, transportation, telephone use, shopping, laundry, medication management) and defined as impairment in 1 categories.

Results Socio-demographic, anthropometric and lifestyle characteristics HIV-positive (N=2982) Gender, n (%) Female 951 (31.9%) Age in years, median (IQR) 49 (45, 54) BMI (kg/m 2 ), median (Q1, Q3) 23.5 (21.4, 26.0) Waist (cm), median (Q1, Q3) 87 (81, 94) Smoking, n (%) No smoking 1756 (58.9%) 1-10 cigarettes per day 516 (17.3%) >10 cigarettes per day 672 (22.5%)

HIV-specific characteristics HIV-positive (N=2982) Likely route of transmission, n (%) Homosexual sex 881 (29.5%) CDC classification C, n (%) 699 (23.4%) Years since HIV diagnosis, median (Q1, Q3) 19.7 (12.8, 24.4) Currently on cart, n (%) 2810 (92.5%) Duration of cart (years), median (Q1, Q3) 5.2 (2.6, 7.8) Currently on NRTIs, n (%) 2319 (82.5%) Currently on PIs, n (%) 1550 (55.2%) Currently on NNRTIs, n (%) 1103 (39.3%) Currently on other drugs, n (%) 569 (20.6%) CD4 count (cells/µl), median (Q1, Q3) 648 (474, 841) Nadir CD4 count (cells/µl), median (Q1, Q3) 200 (86, 300)

Prevalence of comorbidities MHMC (N=2982) Cardiovascular disease, n (%) 142 (4.8%) Hypertension, n (%) 1088 (36.5%) Impaired Fasting Glucose, n (%) 602 (20.2%) Type 2 Diabetes, n (%) 393 (13.2%) Lipodystrophy, n (%) 2265 (76.0%) Dyslipidaemia, n (%) 2449 (82.1%) NAFLD, n (%) 701 (23.5%) Renal Insufficiency, n (%) 284 (9.5%) CKD, n (%) 28 (0.9%) Liver cirrhosis, n (%) 352 (11.8%) Vitamin D insufficiency, n (%) 2061 (69.1%) Osteoporosis, n (%) 269 (9%) COPD, n (%) 91 (3.1%) Any AIDS malignancy, n (%) 77 (2.6%)

Prevalence of comorbidities MHMC (N=2982) ATHENA (N=10278) Cardiovascular disease, n (%) 142 (4.8%) 372 (4%) Hypertension, n (%) 1088 (36.5%) 2379 (23%) Impaired Fasting Glucose, n (%) 602 (20.2%) Type 2 Diabetes, n (%) 393 (13.2%) 578 (6%) Lipodystrophy, n (%) 2265 (76.0%) Dyslipidaemia, n (%) 2449 (82.1%) NAFLD, n (%) 701 (23.5%) Renal Insufficiency, n (%) 284 (9.5%) CKD, n (%) 28 (0.9%) 1399 (14%) Liver cirrhosis, n (%) 352 (11.8%) Vitamin D insufficiency, n (%) 2061 (69.1%) Osteoporosis, n (%) 269 (9%) 829 (8%) COPD, n (%) 91 (3.1%) Any AIDS malignancy, n (%) 77 (2.6%) 765 (7%)

FI distribution at MHMC Distribution of frailty index scores at first visit. Bars represent 0.01 frailty index score groupings. Solid line indicates normal distribution. Average frailty index score at each age. Lines represent exponential best fit. Solid line is men, dashed line is women. Guaraldi G. AIDS. 2015 Aug 24;29(13):1633 41.

Observed (red area) and projected age distribution of HIV-infected patients Age <35 35-49 50-64 65-74 >75 Geriatric Age categories 65-7 yrs >74 yrs 2016 3.8% 0.5%

Observed (red area) and projected age distribution of HIV-infected patients Age <35 35-49 50-64 65-74 >75 Geriatric Age categories 65-7 yrs >74 yrs 2016 3.8% 0.5% 2020 5.7% 0.8

Observed (red area) and projected age distribution of HIV-infected patients Age <35 35-49 50-64 65-74 >75 Geriatric Age categories 65-7 yrs >74 yrs 2016 3.8% 0.5% 2020 5.7% 0.8 2025 14.4% 1.4%

Observed (red area) and projected age distribution of HIV-infected patients Age <35 35-49 50-64 65-74 >75 Geriatric Age categories 65-7 yrs >74 yrs 2016 3.8% 0.5% 2020 5.7% 0.8 2025 14.4% 1.4% 2030 32.9% 4.1% In 15 years time the HIV geriatric population will increase from 4% to 37%

Observed (red area) and predicted burden of Frailty in HIV-infected patients between 2009 and 2030 as simulated by the model Frailty categories Frail FI: 0.3-0.4 Most Frail FI>0.4 2016 32.8% 24.5% 2020 31.3% 38.2% 2025 29.5% 43.6% 2030 28.0% 48.2% In 15 years time the most frail HIV population will increase from 24% to 48%

Observed (red area) and predicted burden of Falls in HIV-infected patients between 2009 and 2030 as simulated by the model Falls 2016 20.4% 2020 21.9% 2025 25.3% 2030 29.8% In 15 years time 30% of PLWH will experience a geriatric syndrome

Observed (red area) and predicted burden of IADL in HIV-infected patients between 2009 and 2030 as simulated by the model IADL>1 2016 22.2% 2020 22.3% 2025 26.3% 2030 33.7% In 15 years time 34% of PLWH will be disable

Discussion HIV and ageing epidemic is far beyond than a simple age shift or an increase prevalence in agerelated comorbidities. The increasing numbers of older patients with frailty, falls and disability depict an geriatric -HIV scenario. When Multi-morbidity is the norm, frailty and disability turn to be relevant clinical outcomes and allows patient risk stratification and tailored clinical interventions We believe that our results can be generalised to other high-income countries with mature epidemics and good access to HIV care.

Study limitations The relationship between age and gender, falls and disability, was postulated to constant over time The model does not simulate the heterogeneity of lifestyle factors (eg, diet, smoking, and exercise) or effect of individual antiretroviral drug use on the development of Frailty Falls and Disability were modeled on the basis of age projection and not (yet) stratified by FI categories

The Geriatric-HIV model Clinical Implications Geriatricians and occupational therapist must be part of the interdisciplinary team taking care of HIV patients The Comprehensive Geriatric Assessment may introduce in HIV care a Multi-dimensional approach which include patients related outcomes, QoL, neurocognitive impairment, physical function, geriatric syndromes. Patient visit diversification must be built in an individualised management plan focused on quality of life and prevention of disability

The Geriatric-HIV model Research Implications Lack of disability should be used to compare healthy life-expectancy in HIV cohorts in comparison to the general population. HIV-infected population has been largely ignored, with most Randomised trials of ART have ignored older patients or excluding people with multimorbidity. Physical function (SPPB) cognitive function (MoCA) and frailty (FI and Frailty Phenotype) can be used in RCT to stratify patient characteristics. QoL, geriatric syndromes and disability may be used as clinical end points in HIC clinical trials

The Geriatric-HIV model INTERPRETATION To our knowledge, this is the first model that has quantified burden of disease. In addition to demographic projections for a developed country with an ageing epidemic the model captures the key factors affecting clinical care of HIV-infected patients, including Frailty, geriatric syndrome and disability providing evidence for the development of new clinical and research intervention for PLWH.

The new target 90-90-90-90-90 90% diagnosed 90% on treatment 90% virally suppressed 90% fit at 90 years Thank you. and stay fit! Conceptual slide - based on Expert Opinion of the presenter