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RESEARCH THEME THREE

Understanding the basic science of HIV in persistence and co-morbidities

Project Leads: Professor Patrick Kennedy, Dr John Thornhill

Overview

Despite effective treatment using antiretroviral therapy (ART), some people living with HIV still have problems with their immune system, known as chronic inflammation. This can cause other health conditions, such as cancer, liver and heart disease, and may also make curing HIV more difficult.

In HIV-1, damage to the gut immune system results in a leaky gut, which is thought to drive chronic inflammation. This damage is less in a related but different type of HIV infection called HIV-2. The SHARE research investigates the differences in gut immunology and the causes of chronic inflammation in HIV-1 and HIV-2 and aims to develop strategies to reduce it.

SHARE is also studying the heightened risk of cirrhosis, liver failure, liver cancer and other health conditions in people who have both HIV and Hepatitis B.

Many of the people living with HIV have been under-represented in HIV studies to date. It’s our goal to address this inequity by giving our local community the opportunity to take part in this in-depth research. Their lived experience will help us to understand the basic science of HIV and make vital improvements to care.”

Professor Patrick Kennedy, Professor of Translational Hepatology, Queen Mary University of London

Activities

SHARE will investigate immune dysfunction and viral markers in HIV and HIV-Hepatitis B co-infection and determine their roles in the persistence and progression of the disease. To achieve this, we are:
  • Conducting studies that investigate virological and immunological factors within racially minoritised populations in the East End of London.
  • Exploring the relationship between HIV and other health problems, such as chronic immune activation HIV-2 and Hepatitis B co-infection.
  • Establishing laboratory capacity and developing a tissue bank to study the neglected disease HIV-2.

Publications

Martin GE, Sen DR, Pace M, Robinson N, Meyerowitz J, Adland E, Thornhill JP, Jones M, Ogbe AT, Parolini L, Olejniczak N, Zacharopoulou P, Brown H, Willberg C, Nwokolo N, Fox J, Fidler S, Haining WN, Frater J. Epigenetic features of HIV-induced T-cell exhaustion persist despite early antiretroviral therapy. Front Immunol. 2021 (in press)

Thornhill J, Orkin C. Long-acting injectable HIV therapies: the next frontier. Curr Opin Infect Dis. 2021 Feb 1;34(1):8-15. doi: 10.1097/QCO.0000000000000701. PMID: 33337617.

Gupta RP, Peppa D, Hill A, Gálvez C, Salgado M, Pace M, McCoy L, Griffith S, Thornhill JP, et al. Evidence for HIV- 1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post-analytical treatment interruption: a case report. Lancet HIV. 2020; S2352-3018(20)30069-2. doi:10.1016/S2352-3018(20)30069-2

Fidler S, Stöhr W, Pace M, Dorrell L, Lever A, Pett S, Kinloch-de Loes S, Fox J, Clarke A, Nelson M, Khan M, Thornhill JP, et al. Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial. Lancet. 2020;395(10227):888-898. doi:10.1016/S0140-6736(19)32990-3

Martin GE, Pace M, Shearer FM, Zilber E, Hurst J, Meyerowitz J, Thornhill JP, et al. Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion. J Infect Dis. 2020;221(7):1135-1145. doi:10.1093/infdis/jiz563

Thornhill JP, Lynch KD, Skelton JK, et al. Vedolizumab use and the associations between α4β7 expression and HIV reservoir in the gut during treated primary HIV infection. AIDS. 2019;33(14):2268-2271. doi:10.1097/QAD.0000000000002344

Thornhill JP*, Pace M*, Martin GE*, et al. CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype. Mucosal Immunol. 2019;12(5):1212-1219. doi:10.1038/s41385-019-0180-2

Thornhill JP*, Martin GE*, Pace M*, et al. CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA. Front Immunol. 2018;9:928. Published 2018 May 4. doi:10.3389/fimmu.2018.00928

Seers T, Vassallo P, Pollock K, Thornhill JP, Fidler S, Foster C. CD4:CD8 ratio in children with perinatally acquired HIV-1 infection. HIV Med. 2018;19(9):668-672. doi:10.1111/hiv.12642

Fidler S, Lewis H, Meyerowitz J, Kuldanek K, Thornhill JP, et al. A pilot evaluation of whole blood finger-prick sampling for point-of-care HIV viral load measurement: the UNICORN study. Sci Rep. 2017;7(1):13658. 2017 Oct 20. doi:10.1038/s41598-017-13287-2

Thornhill JP, Fidler S, Klenerman P, Frater J, Phetsouphanh C. The Role of CD4+ T Follicular Helper Cells in HIV Infection: From the Germinal Center to the Periphery. Front Immunol. 2017;8:46. Published 2017 Jan 30. doi:10.3389/fimmu.2017.00046

Fidler S, Olson AD, Bucher HC, Fox J, Thornhill JP, et al. Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection. J Acquir Immune Defic Syndr. 2017;74(2):126-133. doi:10.1097/QAI.0000000000001220

Thornhill JP, Inshaw J, Kaleebu P, et al. Brief Report: Enhanced Normalisation of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection. J Acquir Immune Defic Syndr. 2016;73(1):69-73. doi:10.1097/QAI.0000000000001013

Hurst J, Hoffmann M, Pace M, Williams JP, Thornhill JP, Hamlyn E, et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat Commun. 2015;6:8495. Published 2015 Oct 9. doi:10.1038/ncomms9495

Thornhill JP, Frater J, Fidler S. Post-treatment control: a functional cure for HIV. Future Virology 10(11): 1245-1256.

Thornhill JP, Fidler S, Frater J. Advancing the HIV cure agenda: the next 5 years. Curr Opin Infect Dis. 2015;28(1):1- 9. doi:10.1097/QCO.0000000000000123

Thornhill JP, Sivaramakrishnan A, Orkin C. Pneumococcal vaccination in people living with HIV. Vaccine. 2015;33(28):3159-3160. doi:10.1016/j.vaccine.2014.07.086

Thornhill JP, Mandersloot G, Bath R, Orkin C. Opt-out HIV testing in adult critical care units. 2014 May 17;383(9930):1720]. Lancet. 2014;383(9927):1460. doi:10.1016/S0140-6736(14)60711-X

Thornhill JP, Aboud M. Timing of antiretrovirals in opportunistic infections. Int J STD AIDS. 2012;23(10):760.doi:10.1258/ijsa.2012.012090

Get in touch

If you’d like more information about research theme three, please contact the project leads:

Professor Patrick Kennedy
Email p.kennedy@qmul.ac.uk

Dr John Thornhill
Email john.thornhill2@nhs.net

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RESEARCH THEME TWO

Driving optimal engagement with care to secure the best health outcomes for people living with HIV

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RESEARCH THEME FOUR

Exploring the bigger picture to achieve health equity

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