HIV Molecular Research Group

Group Overview

Established in 2008, the HIV Molecular Research Group (HMRG) is internationally recognized for its translational research into long-term co-morbidities associated with HIV infection and its treatment with antiretrovirals and re- search into models of testing to increase early diagnosis of HIV.

The HMRG, based on the Mater Misericordiae University Hospital (MMUH) campus, coordinates international, collaborative, translational research in HIV. The group comprises researchers with laboratory, statistical and clinical re- search expertise and is funded through a number of streams including Science Foundation Ireland, the Health Research Board and several industry supporters.

Research Focus

The group's research focuses around four principal themes:

  1. Models of HIV Detection
  2. Bone Disease in HIV
  3. Cardiovascular Disease and HIV
  4. HIV Immunology

Director Profile | Prof Paddy Mallon

  Paddy Mallon

Prof Paddy Mallon

Associate Professor in Medicine, Consultant in Infectious Diseases & Group Head, HIV Molecular Research Group

Experienced clinician academic who has pursued a career in academic medicine with a vision to produce internationally recognised,patient-orientated research that complements and improves delivery of the highest standards of patient care through a work ethic based on the pursuit of excellence. HMRG research highlights include the establishment of the largest, international, prospective cohort of diverse people with and without HIV (>500 participants) examining issues around bone disease, and implementation of one of the largest European emergency department-based HIV screening research programmes, with over 14,000 subjects recruited, and the establishment of the Mater ID/HIV Cohort Study with >1300 participants recruited to date. The HMRG also participates in numerous international collaborative trials, such as the START Study and the NEAT001 study. The HMRG has attracted significant funding from both Science Foundation Ireland and the Health Research Board together with funding from pharmaceutical companies including Merck Sharp and Dohme, GlaxoSmithKline, Gilead and Pfizer.

INTERNATIONAL Conference Involvement or invited Presentations (2014 - 2017) 

  • 24th Conference on Retroviruses and Opportunistic Infections, 2016. Scientific Committee Member
  • 16th European AIDS Conference / EACS, Milan, October 25- 27, 2017. Scientific Committee Member
  • 13th International Congress on Drug Therapy in HIV Infection, 24-26 October 2016, Glasgow. Session Chair
  • 21st International AIDS Conference, Durban, South Africa, 2016. Abstract reviewer.
  • 23rd Conference on Retroviruses and Opportunistic Infections, 2016. Scientific Committee Member.
  • 15th European AIDS Conference / EACS in Barcelona from October 21-24, 2015.Scientific and Programme Committee Member
  • 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, 2015, Abstract reviewer.
  • 12th International Congress on Drug Therapy in HIV Infection, 22-6 November 2014, Glasgow. European AIDS Clinical Society Clinical Session Organiser and Session Chair.
  • 20th International AIDS Conference, Melbourne, Australia. July 20-25, 2014. Abstract reviewer.
  • 2014 International Symposium HIV & Emerging Infectious Diseases (ISHEID), Marseilles, May 21-23, 2014. Abstract Reviewer Presentations
  • Bone disease in treated HIV infection.’ 23rd Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 22-26th 2016
  • ‘HIV and Cardiovascular Disease – do we really understand the risk?’ Australasian HIV&AIDS Conference 2015 (26th Annual Conference of the Australasian Society for HIV Medicine), Brisbane, Australia. September 16-18th 2015
  • ‘Update on Lipodystrophy.’ Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington DC, September 5-9th 2014
  • ‘Getting to the HAART of HIV and Cardiovascular Disease’ The Australian Health and Medical Research Congress, Melbourne, 16-19 November 2014.
  • ‘More than pills: what do people with HIV need to live a long and healthy life?’ British HIV Association Autumn Conference, London, UK. October 9-10th 2014.
  • ‘Ageing and HIV’ 2014 International Symposium HIV & Emerging Infectious Diseases (ISHEID), Marseilles, May 21-23, 2014.

Our Research Themes

The groups research focuses around four principal themes: 

Models of HIV Detection

The Mater-Bronx Rapid HIV Testing Project. M-BRiHT involves collaborations between UCD, MMUH and the Jacobi Medical Centre in the Bronx, New York. M-BRiHT explores the acceptability and feasibility of implementing unselected rapid HIV screening with a novel computer-based video counselling programme in hospital Emergency Departments over 3 sites – the MMUH in Dublin, Manchester in the UK and Catania in Italy. M-BRiHT demonstrates the feasibility of implementing large-scale, population-based HIV screening within a European ED. 14,000 participants have been recruited to date with overall high population prevalence (2.08/1000 new infections) and high completion rates (89.6%). The computer-based video counselling and risk assessment interface has been produced in 2 dialects of English as well as Italian

Bone Disease in HIV

The HMRG coordinates the ‘UPBEAT’ study which examines the pathogenesis of osteoporosis and low bone mineral density in people with HIV. UPBEAT, one of the largest studies of its kind internationally, has followed a cohort of people both with and without HIV for the past five years and has come up with several important findings.

  • Since 2011, the HIV UPBEAT study has enrolled over 500 individuals, approximately half of whom are living with HIV, over a period of 5 years to compare their BMD and other tests related to bone health. Once a year, participants complete a questionnaire about their health; they receive a DXA scan and laboratory testing.
  • By comparing the results we have so far, we found that people with HIV have lower bone mineral density and higher bone turnover, a test that shows how much the tissue in bone leaves the skeleton. However, a more recent analysis has shown that bone density in those with HIV changes at the same rate as those without HIV, which is reassuring that once people with HIV are on stable antiretroviral treatment that they do not seem to lose bone at any faster rate than those without HIV.
  • As we continue this important study, we hope to learn more about the connection between HIV and bone health. This information will help healthcare providers better understand how to prevent, test and treat low BMD in people living with HIV so that we can maintain health over the long term.
  • The HMRG is also investigating novel treatments to prevent bone loss in people with HIV. The APART Study is an international, multisite study funded by the Health Research Board that aims to explore whether a commonly used cheap treatment to prevent bone loss can stop bone loss with initiation of antiretroviral therapy in people with HIV. This study hopes to report findings in 2018.

Cardiovascular Disease (CVD) and HIV

1. People living with HIV have immune activation that contributes to the pathogenesis of cardiovascular disease.

Work completed by HMRG has shown that people with HIV have an activated immune system that is not corrected with antiretroviral therapy and that this immune activation is characterised by abnormalities linked to increased risk of cardiovascular disease.

2. Cells of people living with HIV have signals which suggest abnormal cholesterol metabolism.

Cells called monocyte / macrophages, important in the pathogenesis of cardiovascular disease, contribute to atherosclerosis by retaining cholesterol which then becomes embedded in the walls of blood vessels. Work led by HMRG involving research sites in Dublin, London and Amsterdam has shown that in people with HIV, monocytes have an abnormal gene signature that suggests their cells have too much cholesterol and these abnormalities are not corrected with antiretroviral treatment. These findings have identified specific targets that may be used in the treatment of these abnormalities in people with HIV.

3.  Some antiretroviral treatments may also alter the risk of cardiovascular disease.

Ground-breaking research conducted by HMRG scientists in collaboration with scientists from the Royal College of Surgeons in Ireland have identified an association between a commonly used antiretroviral drug and activity of platelets, which are important in how the blood clots. Abnormalities in platelet function may increase an individual's risk of heart disease and these findings may explain observations from large international studies linking use of this drug with increased cardiovascular disease. 

HIV Immunology

Through the UCD-ID Cohort Project, the HIV Immunology Study supported by a number of industry partners aims to explore additional tests that better reflect and predict immune responses to antiretroviral therapy. This study, in collaboration with Rush University Medical Centre in Chicago, has recruited over 200 subjects. We also conducted a cross-sectional study that provides important and new insights into the potential role of CD4+ and CD8+ T-cell subpopulations in immunological responses in HIV.

 

 

Research Team

Prof Paddy Mallon

Associate Professor in Medicine / Consultant in Infectious Diseases

Prof Jack Lambert

UCD Clinical Professor / Consultant in Infectious Diseases

 Assoc Prof Aoife Cotter

Associate Clinical Professor / Consultant in Infectious Disease

Dr Eoin Feeney

UCD Clinical Lecturer / Consultant in Infectious Diseases

Prof Gerard Sheehan 

Associate Professor in Medicine/ Consultant in Infectious Disease

 

Associated Researchers

Internal (UCD):

  • Dr. Eoin Kavanagh, School of Medicine and Mater Misericordiae University Hospital.
  • Professor Patrick Walsh, Professor of International Development Studies, Geary Institute
  • Dr. Peter Doran, Scientific Director Clinical Research Centre, School of Medicine
  • Dr. Maria Fitzgibbon, Department of Biochemistry, Mater Misericordiae University Hospital
  • Dr. Virginie Gautier, Centre for Research in Infectious Diseases (CRID), School of Medicine
  • Prof Gil Lee, Stokes Professor of Physical Chemistry, School of Chemistry
  • Dr. Aurelia Fabre, School of Medicine

National:

  •  Professor Dermot Kenny, Royal College of Surgeons in Ireland.
  • Professor Colm Bergin, Trinity College Dublin and St James’ Hospital.
  • Professor Mary Horgan, University College Cork.
  • Prof Geraldine McCarthy, Mater Misericordiae University Hospital and Royal College of Surgeons in Ireland.
  • Dr. Gillian McMahon, Dublin City University
  • Professor Sam McConkey, Royal College of Surgeons in Ireland

 

International Collaborators

  • Professor Peter Reiss, Academic Medical Centre, University of Amsterdam, the Netherlands.
  • Professor Jacqueline Capeau, Faculte de Medicine St. Antoine, Paris, France
  • Professor Francesc Villarroya, University of Barcelona, Spain
  • Professor Pere Domingo, University of Barcelona, Spain
  • Professor David Cooper, National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
  • Dr Mark Boyd, Kirby Institute, University of New South Wales, Sydney, Australia
  • Professor Patrick Yeni, University Diderot, Paris, France
  • Dr. Ruth Goodall, Medical Research Council, United Kingdom
  • Professor Juliet Compston University of Cambridge School of Medicine and Addenbrooke’s NHS Trust, England.
  • Dr Ian Williamson, Mortimer Market Centre, University College London.
  • Professor Caroline Sabin, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, London.
  • Dr Marta Boffito, St Stephens AIDS Trust, Chelsea and Westminster Hospital, London.
  • Dr Alan Winston, Department of HIV Medicine, Imperial College Healthcare NHS Trust, London.
  • Dr Frank Post, Kings College London
  • Professor Praphan Phanuphak, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
  • Professor Yvette Calderon, Jacobi Medical Centre, Albert Einstein School of Medicine, Bronx, New York.
  • Professor Giuseppe Nunnari, Università degli Studi di Messina, Sicily, Italy
  • Dr Andrew Ustianiowski, North Manchester General Hospital, United Kingdom.
  • Professor Alan Landay, Rush University Medical Centre, Chicago

HIV and Aging (POPPY study)

Pharmacokinetic and Clinical Observations in People over Fifty (POPPY)

HIV and Ageing

When HIV/AIDS was first described in the 1980’s there was low life expentency for those who contracted the virus. With the availability of better antiretroviral treatment and access to healthcare there is a welcome increase in the number of people living with HIV over the age of 50 and into later life. With improved life expectency there is long term health and well-being issues associated with antiretroviral medication and immune system activation that is not observered in the HIV negative population. 

Study Description

The HIV Molecular Research Group is taking part in the international HIV  POPPY study. The Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) is a prospective, observational study that is examining the effects of ageing on the clinical outcomes of people living with HIV in Ireland and England.

The study describes the incidence and outcomes of co-morbidities in older-HIV-positive people and their relationship with health and lifestyle. The study will contribute to the development and implementation of evidence-based recommendations for the clinical monitoring of older HIV-positive patients especially around osteoporosis and bone health, cerebral function and cognitive impairment, renal function and kidney disease and musculoskeletal pain

Study Ojectives 

Our study describes the impact of advancing age on the experience of living with HIV in Ireland and England. To address this we are establishing cohorts of people with and without HIV aged over 50 and under 50 years old.

To be eligible for the HIV-positive cohort:

  • documented HIV infection
  • age >50 years at study entry
  • self defined white or black African ethnicity
  • likely route of HIV acquisition via sexual exposure

To be eligible for the HIV-negative cohort:

  • documented negative HIV test at study screening
  • age >50 years at study entry
  • self defined white or black African ethnicity

We are particularily interested in older HIV negative gay men to join our study.

Study Visits and Procedures 

Health and Lifestyle 

The research nurse will obtain written informed consent and will record your lifestyle and medical history and a physical examination. You will answer some questions on your quality of life and socio-economic status along with your fracture, fraility and falls risk assessment.

Neurocognitive testing for specific memory and cognitive testing assessing cortical and sub-cortical function as well as a reading test. A simple walking test for speed over a short distance and hand grip strength will also be measured. There is no study medication involved in this study.

Bone and Density Dexa Scan 

We will perform a bone density dexa scan to determine which factors have an impact on bone quality by assessing changes in bone mineral density (BMD). This is important in determining osteopenia and osteoporosis that develops in older people especially those who have HIV.

Blood Samples

A small amount of blood will be taken from you to perform clinical blood tests that will include a liver, kidney, bone, and suger profile along with sexual health check.

This study will include a pharmacokinetic blood sample. “Pharmacokinetics” is the study of the various actions a drug takes within our body. We can analyse this by taking a blood sample and seeing how a drug interacts with it. We will also take a sample of urine and blood for storage but they will only be used for future projects around age-related diseases that are part of the study. 

Lists of Grants

Mallon:

  • Wellcome Trust ‘Wellcome – Health Research Board Irish Clinical Academic Training Programme’. 2016-2023. €9,112,527. PI = Gill. Co-applicant (deputy director) =Mallon.
  • National Institutes of Health (US). ‘Sleep, Ageing, and HIV Infection Cohort Study; POPPY Sleep’ 2016-2020. US$ 600,000 /year over 4 years). PI = Kunisaki. Award to UCD US$256,358. Co-applicant (funded) = Mallon.
  • GlaxoSmithKline Ireland. 'Tolerability, adherence and efficacy of single tablet Dolutegravir / Abacavir / lamivudine antiretroviral therapy in injection drug users.' 2016-2020. €705,628.75 PI=Mallon.
  • EU Horizon 2020 Marie Sk?odowska-Curie Co-funding of regional, national and International programmes (MSCA COFUND 2014). ‘TOPMed10 Fellowship Programme supporting Career Development and Interdisciplinary Training in Omics driven Personalised Medicine.’ Grant agreement no: 666010. Award: € 885,000. PI=Kolch. Funded post-doctoral researcher (Dr Willard Tinago, supervisor Mallon)
  • Gilead Sciences. ‘GS-US- 311-1717 Platelet sub-study’. 2015-2020. €1,224,514 PI=Mallon.
  • Health Research Board Definitive Intervention Award. “Alendronate for Prevention of Antiretroviral Therapy-associated bone loss (APART Study)”(HRA-DI- 2014-701). 2014-2018. €795,667. PI=Mallon.
  • Janssen Cilag / ViiV Healthcare / Gilead Sciences / Bristol Myers Squibb. ‘POPPY – Pharmacokinetic and Clinical Observations in People over fifty’ Award £1800 000, 2013- 2018. Award to UCD .PIs = Winston / Sabin. Award to UCD UK£ . Co-applicant (funded) = Mallon.
  • Gilead Sciences. Expanded HIV testing. ‘Utilisation of the M-BRiHT model to increase community engagement of at risk groups currently not accessing screening.’ 2013-2014. €38,000. P.I. = Mallon.

Lambert:

  • EU Horizon 2020 & HSE. The HepCare Europe project 2016 – 2019. €1,800,000