I nuovi scenari nella gestione di HIV : Invecchiamento e cronicità. Laura Sighinolfi U.O.Malattie Infettive Azienda Ospedaliero-Universitaria Ferrara

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1 I nuovi scenari nella gestione di HIV : Invecchiamento e cronicità Laura Sighinolfi U.O.Malattie Infettive Azienda Ospedaliero-Universitaria Ferrara Bologna, 12 dicembre 2016

2 Infezione HIV 30 anni dopo cosa è cambiato? Epidemiologia : infezione a prevalente trasmissione sessuale Terapia antiretrovirale : inizio precoce terapia farmaci efficaci e ben tollerati cronicizzazione della infezione

3 Probability of Survival Survival is improved but a Discrepancy Still Remains Compared With Uninfected Controls 1.00 Survival of persons with and without HIV infection from 25 yrs of age in Denmark, Population controls Late cart ( ) Early cart ( ) Pre-cART ( ) Yrs of Age Lohse N, et al. Ann Intern Med. 2007;146:87-95.

4 Lohse et al. Data

5 Cause of death, n= 813 3,1% 1,8% 4,8% 5,2% 7,5% 10,3% 12,2% Drug abuse Suicide Cardio-cerebro-vascular 17,0% Non HIV related infections Non-AIDS malignancies (excluded HCC) Unknown 38,1% Other Hepatic HIV related Jun2016 Report

6 The Challenges of Managing the Aging HIV-Infected Patient clinicaloptions.com/hiv Changing Patterns of the Causes of Death in the Swiss HIV Cohort Causes of Death in Participants in the Swiss HIV Cohort Study in 3 Different Time Periods, and in the Swiss Population in 2007 Proportion 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Swiss 2007 Yrs of Death of HIV-Positive Persons vs Swiss Population Weber R, et al. HIV Med. 2013;14: AIDS Non-AIDS malignancy Non-AIDS infection Liver Heart CNS Kidney Intestine/pancreas Lung Suicide Substance use Accident/homicide Other Unknown

ATHENA: Observational cohort of 10,278 HIV-positive pts in the Netherlands Modeling study projections: Proportion of HIV-positive pts 50 yrs of age to increase from 28% in

7 ATHENA: Observational cohort of 10,278 HIV-positive pts in the Netherlands Modeling study projections: Proportion of HIV-positive pts 50 yrs of age to increase from 28% in 2010 to 73% in 2030 Median age of HIV-positive pts on combination ART to increase from 43.9 yrs in 2010 to 56.6 yrs in 2030 Smit M, et al. Lancet Infect Dis. 2015;15:

8 Probability of Survival Decreased Life Expectancy in Older HIV+ Adults in Modern ART Era HIV-Negative Controls HIV-Positive Pts Age (Yrs) Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:

9 Risk (%) Risk (%) Risk (%) Risk (%) Risk (%) HIV Pts More Likely to Experience Bone Fractures, CVD, Diabetes, Renal Failure Bone Fractures 0 < > 60 Age (Yrs) Diabetes 60 0 < > 60 Age (Yrs) < Age (Yrs) > 60 CVD 60 0 < > 60 Age (Yrs) Renal Failure HIV- HIV+ Hypertension 0 < > 60 Age (Yrs) Guaraldi G, et al. Clinicoecon Outcomes Res. 2013;5: Slide credit: clinicaloptions.com

10 Acute MIs per 1000 PYs HIV e rischio CV Rischio IMA è maggiore in HIV-positive pts [1] HIV infection è un fattore di rischio per stroke [2] Maschi HIV nhanno una maggiore prevalenza di placche ateromatose coronariche [1,3] Age (yrs) HIV-negative pts HIV-positive pts 1. Triant VA, et al. J Clin Endocrinol Metab. 2007;92: Chow FC, et al. J Acquir Immune Defic Syndr. 2012;60: Post WS, et al. Ann Intern Med. 2014;160:

11 Pts (%) Comorbidities Increase With Age and With HIV Infection Single-center, case-control study No age-related diseases 1 comorbidity 2 comorbidities 3 comorbidities 4 comorbidities Age, yrs 2+ Comorbidities, % 100 HIV-Infected Pts (n = 2854) HIV-Uninfected Controls (n = 8562) > > *Comorbidites: bone fractures, CVD, diabetes, HTN, hypothyroidism. Guaraldi G, et al. Clin Infect Dis. 2011;53:

12 Aging With HIV THERAPY HIV-Mediated Inflammation Untreated HIV Low CD4 LIFESTYLE Normal Aging Process

13 Relative Hazard of Developing CVD La riduzione dei fattori di rischio CV è efficace anche nei soggetti HIV Effective treatment of modifiable risk factors, such as smoking, cholesterol, and BP can significantly reduce an individual s CVD risk Model for Change in Relative Risk of CVD From Smoking Cessation, Reducing Cholesterol,* or Reducing Systolic BP in a Cohort of 24,323 HIV-Positive Pts Without Prior CVD (D:A:D Study) Reducing systolic BP Reducing cholesterol Smoking cessation Age (Yrs) *Reduced by 1 mmol/l. Reduced by 10 mm Hg. Petoumenos K, et al. HIV Med. 2014;15:

14 Adjusted Relative Risk D:A:D Study: rischio di IMA ed esposizione alla terapia antiretrovirale PIs NNRTIs < > 6 Exposure (Yrs) Friis-Møller, et al. N Engl J Med. 2007;326: Copyright [2007] Massachusetts Medical Society. All rights reserved.

15 % CD38+ HLADR+ CD8+ T Cells Chronic Inflammation Persists in the Setting of Treated HIV Infection T-cell activation higher in treated HIV vs controls [1] 80 Lipopolysaccharide higher in treated HIV vs controls [2] Tissue factor elevated in treated HIV vs controls [3 ] 20 0 HIV + Untreated (n = 82) HIV + ART (n = 65) HIV - (n = 132) 1. Hunt PW, et al. J Infect Dis. 2003;187: Brenchley JM, et al. Nat Med. 2006;12: Funderburg NT, et al. Blood. 2010;115:

16 Factors Contributing to inflammaging in HIV-Positive Pts Traditional Risk Factors ART Toxicity Coinfection Monocyte and macrophage activation Proinflammatory and procoagulant pathways Chronic inflammation Crowe S. IAS 2014 modified. Comorbilities and aging

17 HIV: cronicità ed invecchiamento Gestione assistenziale integrata e multidisciplinare Gestione specialistica diagnostica e terapeutica Valutazione patologie HIV correlate Valutazione multidisciplinare delle comorbilità

18 2030: - 84% of HIV+ pts will have 1 NCD - 28% of HIV+ > 3NCDs - 54% of HIV+ pts will be prescribed meds other than ART

19 HIV: cronicità ed invecchiamento Gestione assistenziale integrata e multidisciplinare Prevenzione delle comorbilità Nuovi farmaci? Nuove strategie terapeutiche?

21 HIV: cronicità ed invecchiamento Gestione assistenziale integrata e multidisciplinare Organizzazione rete polispecialistica e multidisciplinare Integrazione servizi territoriali Supporto sociale Gestione disabilità

22 Frailty, Disability, and Functional Impairment in Older HIV Pts Impairment (body function): Osteoarthritis Limitations (activity): Slow chair rise time, slow gait Frailty (vulnerability): Slow walking speed, low activity, fatigue Disabilities (participation): Requires cane but ramp into home and no stairs in home Impairment: History, exam, x-ray Limitations: Short Physical Performance Battery Timed walk Frailty: Fried s frailty phenotype Disability: Activities of daily living, independent activities of daily living Erlandson KM, et al. Curr HIV/AIDS Rep. 2014;11:

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