Paddy Mallon

Professor of Microbial Diseases

HIV Molecular Research Group

UCD School of Medicine and Medical Science

paddy.mallon@ucd.ie

UCD School of Medicine

& Medical Science

Scoil an Leighis agus

Eolaíocht An Leighis UCD

HIV & Ageing

The POPPY Study

Ageing and HIV

Alvarez-Barco E et al. Curr Opin HIV AIDS. 2016.

A. Accelerated and Accentuated

risk: Cancer occurs earlier in

persons with HIV than uninfected

comparators, and more frequently

B. Accentuated risk: Cancer

occurs at the same ages in the

HIV-infected population, but

more often than among

comparators

Shiels MS, et al. Ann Intern Med 2010:153:452-460.

HIV and Ageing

‘Accelerated or accentuated?’

HIV and ‘Inflammaging’

McGettrick et al. Healthcare . 2018 Feb 14;6(1).

Multicentre, cohort study examining the effects of ageing

on the clinical outcomes of PLWH in UK and Ireland

Objectives:

1. To describe incidence/outcomes of comorbidities in older

PLWH and their relationship with demographic/clinical

factors

2. To develop evidence-based recommendations for the clinical

monitoring of older PLWH

3. To evaluate associations between ARV concentrations and

age, and potential impact of age on efficacy and drug-drug

interactions

The POPPY Study

‘Pharmacokinetic and clinical observations in

people over 50’.

Royal Sussex County Hospital

Mater MisericordiaeUniversity Hospital

Kings College Hospital

HomertonUniversity Hospital

University College Hospital

Royal Free Hospital

St Mary’s Hospital

Chelsea & Westminster

Hospital

POPPY Management:

Alan Winston, Caroline Sabin (co-PIs), Marta Boffito, Paddy Mallon, Memory Sachikonye,

Frank Post.

Statistical team (UCL):

Caroline Sabin, Manolis Bagkeris, Davide de Francesco.

Study Management (Imperial):

Laura Burgess, Daphne Babalis, Paul Greliak

The POPPY Study

PLWH >50 years PLWH <50 years HIV-ve >50 years

• Aged >50 years

• White/black African

ethnicity

• Acquired HIV via

sexual routes

• Aged <50 years

• 150 aged 20-29, 30-39,

40-49 years

• Frequency matched on

gender, ethnicity,

sexual orientation and

clinic

• Aged >50 years

• Frequency matched on

age, gender, ethnicity,

sexual orientation and

geographical location

(in/out London)

POPPY cohort

≥50 PLWH (N=698) <50 PLWH (N=374)≥50 HIV-

(N=304)

Gender, n (%) Female 86 (12.3%) 72 (19.3%) 109 (35.9%)

Male 612 (87.7%) 302 (80.8%) 195 (64.1%)

Ethnicity, n (%) Black-African 95 (13.6%) 75 (20.1%) 31 (10.2%)

White 603 (86.4%) 299 (80.0%) 273 (89.8%)

Age [years], median (IQR) 57 (53, 62) 43 (37, 47) 58 (53, 63)

Sexual

orientationMSM 550 (78.8%) 269 (71.9%) 144 (47.4%)

Heterosexual 148 (21.2%) 105 (28.1%) 160 (52.6%)

Viral load <50 copies/mL, n (%) 641 (92.1%) 323 (86.8%) N/A

CD4+ count [cells/µL], median (IQR) 610 (466, 792) 661 (499, 847) N/A

Nadir CD4+ count [cells/µL], median

(IQR)155 (85, 273) 178 (151, 376) N/A

POPPY cohort characteristics

POPPY – selected studies

POPPY – selected studies (cont.)

Despite ART, people with HIV experience excess rates of

depression when compared to the general population

Depression is associated with several serious health

outcomes, including sub-optimal adherence to ART and

poor retention-in care

Hypothesised explanations include:

- Persistent immune activation

- Coinfections/comorbidities

- ART toxicities

- Living with a stigmatised condition

- Other social/lifestyle/behavioural factors

POPPY – mental health problems

J Int AIDS Soc 19(8Suppl 7): 21487, O215

POPPY - depression

Prevalence of depressive symptoms

≥3

1-2

0

*between diabetes mellitus, CVDs, chest problems, Hepatitis B and C, AIDS events neurological problems,

genitourinary problems, cancer, STDs, joint problems

Association of depressive symptoms with comorbidities*

POPPY - depression

≥3

1-2

0

*including analgesic, antihistamines, antimicrobial, antiplatelet, antiviral, chest, dermatology, endocrine, gastrointestinal, hypertension, lipid lowering, mental health, sleeping pills, neurological, anti-rheumatic/ steroids, supplements, urogenital/STD

POPPY - depression

Association of depressive symptoms with concomitant

medication use*

Comorbidities associated with each component extracted by the PCA with a positive (in green) or negative (in red) correlation greater than 0.4

D De Francesco et al, EACS 2017

Clustering of co-morbidities

“…it’s not the years in your life that

count. It’s the life in your years”Abraham Lincoln

• With the virus now controllable in most of the people living

with HIV (PLWH), HIV management is focusing more on

quality of life (QoL)

• Quality of Life (QoL) is a multidimensional concept that

reflects one´s subjective self-assessment of physical,

emotional and functional status

1. Sabin CA. BMC Med. 2013 Nov 27;11:251. Review,

2. Nakagawa F, et al. AIDS 2012, 3. Miners A, et al. Lancet HIV. 2014

4. Thomas R, et al. Lancet Glob Health 2017. Nov; 5(11):e1133-e1141

Ageing & HIV – maintaining quality life!

D De Francesco et al 2017

Association of depressive symptoms with physical health (SF-36)

POPPY – depression and QOL

D De Francesco et al 2017

Association of depressive symptoms with mental health (SF-36)

POPPY – depression and QOL

Longitudinal analysis of Quality of Life (QoL)

in HIV-positive and HIV-negative subjects

enrolled to the UPBEAT cohort study after 5

years of follow-up

UCD School of Medicine Scoil an Leighis UCD

Mater MisericordiaeUniversity Hospital

E. Alvarez1, A.G. Cotter1,2, C.A. Sabin3, T. McGinty1, S. Babu1, R. Chen4, A. Macken1, J.J. Brady2, E. Kavanagh2, G. McCarthy2, J. Compston5, P.W.G. Mallon1,2, HIV UPBEAT Study

Group

1HIV Molecular Research Group, University College Dublin School of Medicine, Dublin, Ireland, 2Mater

Misericordiae University Hospital, Dublin, Ireland, 3Institute of Global Health, University College London,

London, UK, 4Medical College of Wisconsin, USA, 5Department of Medicine, School of Clinical Medicine,

Addenbrooke’s NHS Trust, University of Cambridge, UK

‘Understanding the Pathology of Bone Disease in HIV-infected

Individuals’: Prospective cohort of HIV-positive and HIV-negative subjects

from similar demographic backgrounds in Ireland with over 5 years of

follow-up

QoL assessments:

QOL & HIV – UPBEAT Study

Alvarez E et al. 19th ADRLH Madrid 2017. Abstract 72.

-16

-12

-8

-4

0

4

PhysicalFunctioning

RolePhysical

Bodily Pain GeneralHealth

Vitality SocialFunctioning

MentalHealth

P=0.01 P=0.02P=0.13

HIV+ HIV-

P=0.25 P=0.88 P=0.53 P=0.70

• Absolute mean change in QoL sub-domain scores

UPBEAT – changes in QOL subdomains

Alvarez E et al. 19th ADRLH Madrid 2017. Abstract 72.

HIV+ vs HIV- Effect on QALY

(B)

95% CI P value

Unadjusted -.473 -3.009 2.063 0.71

Adjusted - Age -2.778 -3.692 -1.863 <0.0001

- Gender, Ethnicity -2.157 -3.078 -1.236 <0.0001

- Socio-economic -2.154 -3.096 -1.213 <0.0001

- smoking -2.058 -3.024 -1.092 <0.0001

- drug use -2.095 -3.096 -1.094 <0.0001

- comorbidities -2.034 -3.046 -1.023 <0.0001

Alvarez E et al. IDSI Galway 2018.

UPBEAT – impact on QALY

HIV-positive status was independently associated with a mean

age-adjusted reduction of 2.8 QALYs (p<0.0001).

p = 0.14

p = 0.83

p < 0.01

p = 0.03 p < 0.0001 p = 0.06

p < 0.0001

20

40

60

80

Attention/Working memory

Executivefunction

Processingspeed

Visualattention

Verbal learning/Memory

Visual learning/Memory

Globalscore

Co

gn

itiv

e d

om

ain

T s

co

re

HIV-status

HIV+

HIV-

BMC Infect Dis. 2016 Oct 28;16(1):617

POPPY - cognitive function

Pool E et al. (submitted)

POPPY – lifestyle clustering

Mental health condition OR (95% CI)

PHQ-9 >5OR (95% CI)

CES-D >16OR (95% CI)

Unadjusted 1.31 (0.91, 1.88) 1.50 (1.02, 2.21) 1.61 (1.08, 2.39)

Adjusted for age 1.30 (0.90, 1.87) 1.49 (1.01, 2.20) 1.66 (1.11, 2.47

Pool E et al. (submitted)

POPPY – lifestyle clustering

Association between high risk phenotype and mental

health/depressive symptoms

POPPY – summary

• POPPY study provides insights into behavioural and

psychosocial aspects associated with living with HIV

• Aspects of worse mental health significantly more common

in PLWH

• Mental health, behaviours and physical health linked – risk

phenotype

• Significant impact on QOL over time

• Ongoing studies to explore underlying pathophysiology

The Co-morBidity in Relation to Aids

(COBRA) Collaboration

POPPY: ‘Pharmacokinetic

and Clinical Observations in

People over Fifty’

COBRA: clinical studies will run as sub-studies of POPPY and AGEhIV:• Collecting the extra information required• Whilst utilising the existing infrastructure

AcknowledgmentsPOPPY Management Team: Daphne Babalis, Marta Boffito, Laura Burgess, Paddy Mallon, Frank Post, Caroline Sabin, Memory Sachikonye, Alan Winston

POPPY Scientific Steering Committee: Jane Anderson, David Asboe, Marta Boffito, Lucy Garvey, Paddy Mallon, Frank Post, Anton Pozniak, Caroline Sabin, Memory Sachikonye, Jaime Vera, Ian Williams, Alan Winston

POPPY Sites and Trials Unit:• Elton John Centre, Brighton and Sussex University Hospital (Martin Fisher, Amanda Clarke, Jaime Vera, Andrew Bexley, Celia

Richardson, Sarah Kirk, Rebecca Gleig)

• St Stephen's Centre, Chelsea and Westminster Hospital (Marta Boffito, David Asboe, Anton Pozniak, Margherita Bracchi, Nicole Pagani, Maddalena Cerrone, Daniel Bradshaw, Francesca Ferretti, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, Clive Matthews, Peter Fernando, Chido Chiwome, Shane Hardwick)

• Homerton Sexual Health Services, Homerton University Hospital (Jane Anderson, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri)

• Caldecot Centre, King’s College Hospital (Frank Post, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Beatriz Santana Suárez)

• HIV Molecular Research Group, School of Medicine, University College Dublin (Paddy Mallon, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sumesh Babu)

• Department of Infection and Population Health, University College London (Ian Williams, Damilola Otiko, Laura Phillips, Rosanna Laverick, Michelle Beynon, Anna-Lena Salz, Abigail Severn)

• St. Mary’s Hospital London, Imperial College Healthcare NHS Trust (Alan Winston, Lucy Garvey, Jonathan Underwood, Lavender Tembo, Matthew Stott, Linda McDonald, Felix Dransfield)

• Imperial Clinical Trials Unit, Imperial College London (Andrew Whitehouse, Laura Burgess, Daphne Babalis)

• Ian Charleson Day Centre, Royal Free Hospital (Margaret Johnson, Nnenna Ngwu, Nargis Hemat, Anne Carroll, Sabine Kinloch, Mike Youle, Sara Madge)

POPPY methodology/statistics/analysis: Caroline Sabin, Davide De Francesco, Emmanouil Bagkeris

Funders: The POPPY study is funded from investigator initiated grants from BMS, Gilead Sciences, Janssen, MSD and ViiVHealthcare.

Acknowledgements

HIV Molecular Research Group /

Department of Infectious Diseases

• Dr Jack Lambert

• Dr Gerard Sheehan

• Dr Eoin Feeney

• Dr Aoife Cotter

• Dr Elena Alvarz Barco

• Dr Tara McGinty

• Dr Padraig McGettrick

• Dr Willard Tinago

• Alejabdro Garcia

• Alan Macken

• Sumesh Babu

• Bindu Krishnanivas

• Aoife McDermott