Paddy Mallon
Professor of Microbial Diseases
HIV Molecular Research Group
UCD School of Medicine and Medical Science
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