PIs are the real world answer for the chronic patient s management. Giovanni Guaraldi

Transcription

1 PIs are the real world answer for the chronic patient s management Giovanni Guaraldi

2 HIV MEDICATION TOXICITY Ageing with HIV: The clinical consequences AGEING Heart disease Kidney disease Liver disease Sarcopenia Osteopenia Cancer Mitochondrial damage Cognitive declines Social problems Emotional problems AGEING WITH HIV Increased probability of comorbidities HIV Heart disease Kidney disease Liver disease Sarcopenia Osteopenia Cancer Mitochondrial damage Cognitive declines Social problems Emotional problems The aging HIV patient is a chronic patient Adapted from Vance DE. Am J Nurs 2010;110:42-47.

3 What do the guidelines recommend for older patients? DHHS: >50 years: 1 Start ART regardless of CD4 because of increased risk of non- AIDS related complications and reduced immunological response Bone, kidney, metabolic, CV, and liver health of older HIV-infected adults should be monitored closely EACS: CVD risk assessment (Framingham score) should be performed in all men >40 and women >50 years 2 Bone disease assessment with FRAX in patients >40 years 2 BHIVA: Consideration should be given to starting at higher CD4 cell counts (i.e. 350 cells/mm 3 ) in older persons 4 CV=cardiovascular; FRAX=WHO Fracture Risk Assessment Tool IAS: Start ART if >60 years regardless of CD4 cell count 4 1. DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available at: Accessed March 2014; 2. EACS Guidelines 2013; Available at: Accessed March 2014; 3. IAS Guidelines 2012; Available at: Accessed March 2014; 4. British HIV Association guidelines November HIV Medicine 2014;15:1 85.

4 Aging, as a health condition FRAILTY Disability Multimorbidity

5 Frailty recognition in clinical practice Frailty Related Phenotype Frailty as a deficit accumulation Fried et al., J Gerontol Med Sc 2001 Rockwood et al. Lancet 1999;353:205-6

6 Frailty recognition in clinical practice Frailty Related Phenotype A person can be said to be frail if they have any 3 of the following features: 1. They move slowly. 2. They have a weak handgrip. 3. They have reduced their level of activity. 4. They have (unintentionally) lost weight. 5. They feel exhausted. pre-frail is used when only one or two of these deficits is present. Clinically recognizable and not otherwise definable as being disabled or as having multiple co-morbid illnesses Frailty as a deficit accumulation Frailty can be operationalized as deficit accumulation and can be expressed in a frailty index. Can be summarised as a scale from Robust to Terminally Ill A frailty index derived from routinely collected clinical data can offer insights into the biology of aging using mathematics of complex systems. Fried et al., J Gerontol Med Sc 2001 Rockwood et al. Lancet 1999;353:205-6

7 Hypothetical association between frailty, HANA and immune activation / inflammation 35 0

8 The patient and his family provided consent to show these Mr. A case study To what extent Age change our clinical practice? 25 yrs CD4=250μL VL=73000/mL 45 yrs CD4=650μL VL<40/mL 65 yrs CD4=250μL VL=73000/mL 75 yrs CD4=650μL VL<40/mL Naive Experienced Naive Experienced

9 Hypothetical association between frailty, HANA and immune activation / inflammation FRAIL WITH HIV PSEUDO- Frail PRE-Frail Robust 350

10 FRAILTY CONCEPT IS NOT FRAILTY MEASURE The choice of your tool is function of the outcome you chose

11 Aging, as a health condition FRAILTY Multimorbidity Disability

12 A novel frailty index predicting outcomes in HIV patients We constructed an HIV frailty index (MMFI) based on routine health variables. OBJ: We hypothesized the HIVFI could predict multimorbidity at any age and HIV characteristics and discriminate between pts in the same age category with different multimorbidity (MM) risk. Methods: retrospective longitudinal study enrolling pts with 2 annual visits Results: Mortality Study: 2739 pts, 55 deaths, PYFU, mortality rate 4.97/1000 PYFU MM Study : 2241 pts, 341 events, 7682 PYFU, Incident Rate (IR) 44.39/1000 PYFU

13 List of variables selected to create the MMFI MMFI index N variable 1 Impaired fasting glucose 2. Lipoatrophy Lipohypertrophy Mixed form 3. NAFLD 4. Menopause Or male hypogonadism 5. MDRD 6 BMI 7. Waist 8. Visceral adipose tissue 9. Sarcopenia 10. Low bone mineral density 11. Insulin resistance 12. Total cholesterol 13. LDL 14. HDL 15. TG 16. HCY 17. WBC 18. HB 19. Fib4 20. HCV+ 21. HBsAg+ 22. VitD insuficiency 23. Polyfarmacy 24. PTH 25. DDimer 26. PCR 27 Sedentary life Age and gender are used as covaraites We excluded variables which were present <80% in each patient visits. Co-morbidities (MM= 2+) 1. CVD (clinical) 2. HTN (measured + drug) 3. T2DM (measured + drug) 4. CKD (measured) 5. Cirrosi (clinical) 6. COPD (measured + clinical) 7. Osteoporosi (DEXA + fracture) 8. Cancers (clinical) Distribution of MMFI in the MHMC 28. TSH MMFI Cut off=0.30 (third quartiles)

14 Age and gender distribution of MMFI

15 Cox analysis to predict Mortality rate 2739 pts, 55 deaths, PYFU, mortality rate 4.97/1000 PYFU

16 Poisson analyses to predict Mm 2241 pts, 341 events, 7682 PYFU, Incident Rate (IR) 44.39/1000 PYFU

17 Risk prediction of MMFI according to Age and Immune Status changes during ART Immune recovery: Nadir CD4<350, Current CD4>500 No-Immune impairment: Nadir CD4>350, Current CD4>500

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19 Mr. B 2007 CD4=329/μL VL=12000 c/ml TDF/FTC+EFV 2010 CD4=543/μL VL<40 c/ml VACS=12 (rischio assente) DRV/r 2014 CD4=741/μL CD4/CD8>1 Vl non detectable DRV/r

20 Antropometry Changes in the FU period

21 Cardio-Metabolic Changes in the FU period 20/6/12 CAC=254 Coronary Age=74 yrs

22 Kidney & Bone Changes in the FU period

23 NRTI options are limited and not always guideline recommended

24 Change of MMFI in the FU period 0,45 0,4 0,39 0,35 0,3 0,25 0,3 0,28 0,2 0,15 0,16 0,1 0,05 Atripla DRV/r 0

25 Hypothetical association between frailty, HANA and immune activation / inflammation MMFI=1 A 2007 MMFI= MMFI=0.30 B MMFI= MMFI=0.14 C 35 0

26 DRV/r based regimen not including NRTI revert age related MMFI increase The aim of the study was to evaluate long term MMFI change in HIVinfected patients with suppressed viremia treated with darunavir/ritonavir (DRV/r) monotherapy (25 pts) versus DRV/r +2NRTI (122 pts). * p=0.04 * *

27 ARV therapy in aging patients Initiate ART in patients > 50 years regardless of CD4 count Regimen choice should be informed by review of co-morbidities, multimorbidity and polyfarmacy Data on the long-term safety of certain ARVs in older people are lacking Monitor for ART-related renal, liver, CV, metabolic, and bone toxicities 1. DHHS Guidelines Available at: Accessed April 2012

28 Hypothetical future Scenario: will frailty improve clinical care and outcomes? Initiate ART in patients > 50 years regardless of CD4 count Regimen choice should be informed by review of FRAILTY, co-morbidities, multimorbidity and polyfarmacy Data on the long-term safety of certain ARVs in older people WILL BE MEASURED WITH FRAILTY INDEX Monitor for ART-related renal, liver, CV, metabolic, bone toxicities AND FRAILTY INDEX 1. DHHS Guidelines Available at: Accessed April 2012