01 GUARALDI TEATRO - icar2017.it · 20/06/2017 13 Guaraldi G, et alPLoS One. 2015 Apr 13;10(4):e0118531 At any age, long-term infected people (ageing patients) had a 5-fold accentuated

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Comorbidities and Aging

Guaraldi Giovanni

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Theorem:

HIV modifies the relationship between

age and comorbidities

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THE CONTEXT: Number of persons living

with HIV aged ≥50 by region (1995-2013)

The Gap Report. Available at: http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Gap_report_en.pdf.

Accessed February 2015

� There are approximately 4.2 million

persons aged ≥50y living with HIV today.

� More than 2 million of which live in sub-

Saharan Africa.

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2000 2005 2010 2014

DrugToxicities

Co-morbidities Multi-morbidities

Frailty

DAY TO DAY MANAGEMENT OF HIV PATIENTS

Disability

2017

Age (years)

ADL-Mobility

Disability

Aging

“Accelerate

d”

65 100

Ph

ysi

cal

Fu

nct

ion

Robust

Frail and pre-frailReversible

DisableADL-MobilityDependence

Aging

“Normal”

Trajectories of physical function in older

subjects

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ARVHIV

Host

ARVHIV

Host

Hp: Age modulate the interaction between HIV, comorbidities, geriatric syndromes and disability

Chronological time

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Age distribution shift in HIV pts attending MHMC

2016: median age 52.2yrs IQR 48-572003: median age 43.4 yrs IQR 39-46

AGE AS A HEALTH CONDITIONThe complex interaction of Age and comorbidities in HIV patients

CoM1

CoM2

MMFrailty

GeriatricSyndromes

DisabilityDependence

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Hasse B et al. CLIN INFECT DIS. 2011;53(11):1130-1139.

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Age

CoM1

CoM2

MMFrailty

Geriatric

SyndromesDisability

Dependence

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Guaraldi G, CLIN INFECT DIS. 2011;53(11):1120-1126.

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Age

HIVCoM1

CoM2

MMFrailty

GeriatricSyndromes

DisabilityDependence

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Age distribution shift in HIV pts attending MHMC

2016: median age 52.2yrs IQR 48-572003: median age 43.4 yrs IQR 39-46

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The pyramid of age in pts attending MHMC is a composite of a diverse population living with HIV since the pre-HAART period or living with HIV since 2006

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Guaraldi G, et alPLoS One. 2015 Apr 13;10(4):e0118531

At any age, long-term infected people (ageing patients) had a 5-fold accentuated risk of multimorbidity than HIV-negative controls, while more recently infected people (aged patients) had an intermediate risk compared with the control group

Pro

bab

ility

of

mu

ltim

orb

idit

y 0.6

0.4

0.2

0

20 30 40 50 60 70Age

HIV aged HIV ageing HIV negative

Risk for Multy-

Morbidity

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Guaraldi G. AIDS Res Ther. January 2017:1-7.

Multivariable logistic regression

model to detect independent

predictors of MM in the cohort

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Age

HIVCoM1

CoM2

MMFrailty

Geriatric

SyndromesDisability

Dependence

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Outline

1. What is unique in the relationship

between age and comorbidities in

people living with HIV (PLWH)?a) One year with HIV impacts on your biological

age more than one chronological year

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OBJ: to compare prevalence and risk factors for frailty, sarcopenia,

disability and QoL in HIV patients living with HIV for more than 20 years

(pre-HAART era) or less than 10 years (contemporary HIV care)

GERIATRIC SYNDROMES IN PATIENTS

ENTERING CONTEMPORARY HIV CARE

FRAILTY

Quality of Life

� EuroQol - EQ-5D-5L

Cut off value<100

DISABILITY

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Objectiveto compare prevalence and risk factors for frailty,

sarcopenia, disability and QoL in HIV patients living with

HIV for more than 20 years (pre-HAART era) or less than

10 years (contemporary HIV care)

Study Hypothesis

Older HIV patients are at increased risk for aging related complications.

We hypothesized that recent seroconvertors starting contemporary HIV treatments may have a reduced prevalence and risk of aging related outcomes, asncompared to patients living with HIV for more than 20 years

SARCOPENIA AND FRAILTY IN PATIENTS

ENTERING CONTEMPORARY HIV CARE

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Materials and methodsWe performed cross-sectional study including consecutive HIV patients having access in 2005-2016 at the Modena HIV Metabolic Clinic

“Contemporary” HIV care model:

� HIV duration: <10 years

� Start ART: >2006

“Old” HIV care model:

� HIV duration: >20 years

� Start ART: <2005

Outcome measuresSARCOPENIA

� Muscle mass (DEXA)

Baumgarten criteria

ASMI <7.26 kg/m2

ASMI <5.45 kg/m2

� Muscle strength

Hand grip assessment below the mean for sex and age

FRAILTY

� Frailty phenotype Fried

criteria >3 out of 5 phenotypic items

� Frailty Index

37-item frailty indexCut off value for frailty >0.38

Disability

� IADL

Cut off value>1

Quality of Life

� EuroQol - EQ-5D-5L

Cut off value<100

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Results

total

"Contemporary" HIV care

(Aged with HIV)

”Old" HIV care

(Aging with HIV) p

828 173(20.89%) 655(79.11%)

Duration HIV 296.5 (256-349) 70 (40-99)) 316 (282-357) <0.01

DEMOGRAPHIC VARIABLES

Women 230 (27.78%) 18 (10.4%) 212 (32.37%) <0.01

Men 598 (72.22%) 155 (89.6%) 443 (67.63%)

Age 52.19 (7.62) 44.84 (9.29) 54.13 (5.72) <0.01

BMI 24.06 (3.93) 25.2 (3.94) 23.76 (3.87) <0.01

Life style

Smoke: pack year 16.5 (4.5-30)) 10.18 (1.01-21.62) 18 (6-30.61) <0.01

Alcohol

None 558 (67.97%) 106 (62.35%) 452 (69.43%) 0.04<20 g/day 387 (46.74%) 79 (45.66%) 193 (29.65%)

>20 g/day 11 (1.34%) 5 (2.94%) 6 (0.92%)

Physical activity

None 355 (42.87%) 66 (38.15%) 289 (44.12%) 0.02

<3 hours/week 387 (46.74%) 79 (45.66%) 308 (47.02%)

>3 hours/week 86 (10.39%) 28 (16.18%) 58 (8.85%)

HIV risk factors

IVDU 247 (29.83%) 2 (1.16%) 245 (37.4%) <0.01

MSM 266 (32.13%) 108 (62.43%) 158 (24.12%)

HIV Partner 246 (29.71%) 45 (26.01%) 201 (30.69%)

Other 69 (8.33%) 18 (10.4%) 51 (7.79%)

HIV variables

CD4 nadir 200 (100-303.75) 309 (209.25-407.25) 188.5 (90.5-290) <0.01

Current CD4

687 (516.75-

876.25) 759 (561-918) 659 (501-868.5) <0.01

CD4/CD8 ratio 0.92 (0.47) 1.01 (0.5) 0.9 (0.46) <0.01

HIV-RNA undetectability 820 (99.03%) 172 (99.42%) 648 (98.93%) 0.88

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Results

total

"Contemporary" HIV care

(Aged with HIV)

”Old" HIV care(Aging with

HIV) p828 173(20.89%) 655(79.11%)

Multi-Morbidity 93 (11.23%) 4 (2.31%) 89 (13.59%) <0.01

Frailty

Frailty Index Score 0.29 (0.1) 0.22 (0.08) 0.31 (0.1) <0.01Frailty Index cathegorical (>0.28) 346 (42.04%) 29 (16.86%) 317 (48.69%) <0.01Frailty Phenotype 24 (2.92%) 1 (0.58%) 23 (3.54%) 0.07

SarcopeniaASMI (Sarcopenia cathegorical) 334 (40.34%) 63 (36.42%) 271 (41.37%) 0.27

Hand Grip - mean (Kg), Dominant hand 35.9 (10.09) 38.59 (9) 35.19 (10.25) <0.01Hand Grip - mean (Kg), Non Dominant hand 34.42 (10.19) 37.74 (8.84) 33.55 (10.34) <0.01

Low HG 327 (39.49%) 112 (64.74%) 215 (32.82%) <0.01Geriatric outcomes

Depression (CESD ) 12 (6-21) 10 (5-18) 13 (6-22) 0.04QoL Impairment 523 (75.8%) 105 (70.95%) 418 (77.12%) 0.15

FALLS 72 (12.2%) 12 (13.79%) 60 (11.93%) 0.75IADL impairment 64 (10.22%) 8 (6.61%) 56 (11.09%) 0.2

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Results

Frailty prediction at multivariable logistic regression analyses

Panel “b”

Panel “a”

Risk for Frailty according

to FI (panel a) and Frailty phenotype (panel b)

OR lower upper p value

Aging vs

Aged 2,94 1,73 5,08 <0.01

Age 1,05 1,02 1,07 <0.01

Male vs

Female 1,36 0,96 1,92 0,08

CD4Nadir 1 1 1 0,19

IVDU 1,37 0,97 1,92 0,07

Moderate

Gym 0,45 0,33 0,61 <0.01

Intensive

Gym 0,15 0,08 0,28 <0.01


Aging vs

Aged 7,99 1,3 159,53 0,06

Age 1 0,93 1,07 0,97

Male vs

Female 1,17 0,47 3,21 0,74

CD4Nadir 1 1 1 0,1

IVDU 0,7 0,26 1,75 0,46

Moderate

Gym 0,31 0,11 0,76 0,02

Intensive Gym 0

1,19518E

+20 0,99

Frailty Index predictors

Frailty phenotype predictors

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ResultsRisk for Sarcopenia according to ASMI (panel a) and hand Grip (panel b)

Sarcopenia prediction at

multivariable logistic regression analyses

Panel “b”

Panel “a”


Aging vs

Aged 1,13 0,7 1,81 0,62

Age 1 0,98 1,02 0,84

Male vs

Female 1,77 1,26 2,5 <0.01

CD4Nadir 1 1 1 0,06

IVDU 1,04 0,74 1,45 0,82

Moderate

Gym 0,7 0,52 0,94 0,02

Intensive

Gym 0,29 0,16 0,51 <0.01


Aging vs

aged 0,72 0,44 1,17 0,18

Age 0,91 0,89 0,94 <0.01

Male vs

Female 2,9 1,99 4,27 <0.01

CD4Nadir 1 1 1 0,23

IVDU 0,69 0,48 0,98 0,04

Moderate

Gym 0,82 0,59 1,13 0,23

Intensive

Gym 0,53 0,31 0,91 0,02

Muscle strength predictors

Muscle mqss predictors

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Results

Risk for disability in patients entering “old” vs “contemporary” HIV care

Disability was defined for >1 item at IADL assessment


Aging vs Aged 1,23 0,45 3,72 0,7

Age 0,99 0,94 1,04 0,68

Male vs Female 0,15 0,08 0,28 <0.01

CD4Nadir 1 1 1 0,44

IVDU 0,8 0,41 1,49 0,48

Moderate Gym 0,69 0,38 1,23 0,21

Intensive Gym 0,63 0,18 1,78 0,43

Disability predictors

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Results

Risk for Impaired QoL in patients entering “old” vs “contemporary” HIV care

QoL impairment was defined for any value <100


Aging vs Aged 0,94 0,52 1,68 0,84

Age 1 0,97 1,03 0,9

Male vs Female 0,81 0,51 1,25 0,34

CD4Nadir 1 1 1 0,28

IVDU 1,63 1,04 2,59 0,04

Moderate Gym 0,59 0,39 0,88 0,01

Intensive Gym 0,23 0,13 0,41 <0,01

QoL predictors

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Age

HIVCoM1

CoM2

MMFrailty

Geriatric

SyndromesDisability

Dependence

HIV

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Outline





b) Older people with HIV have similar geriatric

outcomes regardless duration of HIV infection

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Age at acquisition of HIV affects the risk of

comorbidities after 25 years of infection exposure

The impact of age at acquisition of HIV as an independent predictor for chronic conditions and MM is not known.

• The study objective was to assess the prevalence of, and risk factors for, individual comorbidities and MM between HIV patients with similar duration of HIV infection, but whom acquired HIV at different stages of life.

Group 1 Group 2 Group 3

total 0-25 years 25-50 years 50-75 years p

gruppo 131 32(24.43%) 77(58.78%) 22(16.79%)

age 53.24 (16.42) 27.67 (1.16) 57.12 (2.71) 76.84 (2.63) <0.01

Gender F 45 (34.35%) 13 (40.62%) 29 (37.66%) 3 (13.64%) 0.08

Lipodystrophy yes 87 (69.6%) 20 (76.92%) 46 (59.74%) 21 (95.45%) <0.01

HepB yes 13 (12.5%) 8 (33.33%) 5 (7.94%) 0 (0%) <0.01

HepC yes 42 (40.38%) 1 (4.17%) 40 (63.49%) 1 (5.88%) <0.01

Un-Employed 105 (84.68%) 17 (54.84%) 66 (92.96%) 22 (100%) <0.01

Smoker 39 (31.71%) 5 (16.67%) 33 (46.48%) 1 (4.55%) <0.01

Heavy Drinker 48 (39.67%) 4 (14.29%) 33 (46.48%) 11 (50%) <0.01

IVDU 44 (35.2%) 0 (0%) 44 (57.14%) 0 (0%) <0.01

CDC_Classification C 42 (38.18%) 17 (85%) 18 (26.47%) 7 (31.82%) <0.01

CD4 580 (394.25-705.75) 621 (370-779) 570 (398-689) 611.5 (515.25-727.75) 0.61

VL 40 (40-40) 0 (0-25.5) 40 (40-40) 40 (40-40) <0.01

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Age at acquisition of HIV affects the risk of

comorbidities after 25 years of infection

exposure

�=2.09

p=ns

�=1.01

p=ns

�=11.98

p=0.02

�=16.08

p=0.04

Driver is AgeDriver is HIV

Guaraldi G. ICAR 2017

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Outline





b) Older people with HIV have similar geriatric

outcomes regardless duration of HIV infection

c) Age of HIV acquisition modulates the impact of

HIV duration on global health

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Theorem:

The relationship between age and comorbidities

is UNIQUE, in people living with HIV (PLWH)

CLINICAL IMPLICATION� Patients awareness and education may promote

healthy life styles and successful aging

� Clinical management of aging HIV patients refers to

people with longer HIV exposure, low nadir CD4 or who

acquired HIV at an older age regardless their

chorological age

� These patients must be considered vulnerable to MM, geriatric syndromes and disability

� A multidimensional geriatric-like approach is needed

including proactive switch to less toxic drugs and active

intervention to reduce the risk of polypharmacy

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It is time to move into a proactive approach

in ARV management in older HIV patients

Considerations in Management of ART

in the Older HIV Patient

Guaraldi G., Medskape 2016

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ARV therapy in geraitric HIV patients

In mono/dual therapy for 384 patients, there were 68

different ARV regimens

In the triple/mega group 839 patients, there were

113 different ARV regimens

High prevalence of non

conventional ARV regimens in elderly HIV pateinbts suggeststhat clinicians try to tailor ARV

regimensaccording to age, HIV duration, MM and PP

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GILEAD CONFIDENTIAL. FOR INTERNAL TRAINING USE ONLY. NOT TO BE USED WITH HCPS.

A COMPREHNSIVE DEVELOPMENT AGENDA ON

TAF IN CLINICAL PRACTICE

• When should you definitely use TAF over TDF?

� Patient with low BMD, osteoporosis on DEXA a high risk of major fracture as determined by FRAX

� Patient with renal disease (eGFR>30) or evidence for proximal tubular dysfunction (e.g. proteinuria) or renal toxicity or other intolerance secondary to TDF

� Older adults

� Adolescents or youth

� When the switch is cost-neutral or cost-saving

• When should you definitely not use TAF?

� Patient on rifamycin, phenobarbital, carbamazepine

� Pregnant women until clinical data are available

� For pre-exposure prophylaxis (PrEP)

� TAF does not have a licensed indication for CKD stage 4 or 5

� Patients with proven or suspected resistance to the component drugs in any TAF-containing FDC or STR

35

Di Biagio A et al. Submitted for publication 2017

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The role of TAF in the jungle of ARV

prescription

Geriatrics-focused research end points, including frailty,

geriatric syndromes and physical function, will hopefully

be also used to assess the benefit of ARV strategies,

comparing single tablet regimens with less drug

regimens.

This “game changer” in clinical studies will take some

time, while right now a significant reduction in the

jungle of ARV prescriptions is taking place, with clear

benefits for both patients and prescribers.

Conceptual slide - based on Expert Opinion of the presenter

‡

Documents

01 GUARALDI TEATRO - icar2017.it · 20/06/2017 13 Guaraldi G, et alPLoS One. 2015 Apr 13;10(4):e0118531 At any age, long-term infected people (ageing patients) had a 5-fold accentuated