The main focus of the Lewin group is to understand why HIV infection persists on antiretroviral therapy, to develop new strategies to eliminate latency and to define the biological determinants of immune reconstitution and factors that drive liver disease in HIV-hepatitis B virus co-infection. The laboratory is now also actively involved in COVID in relation to novel diagnostics, the use of primary tissue models and therapeutics using gene editing strategies.
Clinical trials for HIV cure
Our group have had a long standing interest in early phase 1/2 studies to eliminate HIV latency. Initial studies focused on the role of histone deacetylase inhibitors and other latency reversing agents. Our current interventional studies including TLR agonists, neutralising antibodies and anti-PD1. In addition to interventional studies, our lab focuses on observational studies to understand the determinants of HIV persistence, including the role of circadian rhythms, clonal proliferation, co-infections and other clinical parameters.
Virological determinants of HIV persistence and elimination
Our major focus is on unravelling the viral determinants of HIV latency and strategies to either reverse or permanently silence HIV. We use innovative virological techniques to understand how the virus can persist on ART using CD4+ T-cells from people living with HIV on ART. We have a major interest in developing assays to better quantify HIV persistence on antiretroviral therapy. We are aiming to identify new ways to reverse HIV latency and enhance apoptosis including using nanoparticles to deliver drugs or gene editing approaches to the nucleus. This work is done in collaboration with Dr Frank Caruso in the Department of Biomedical Engineering.
Immunomodulation to eliminate the HIV reservoir
HIV can persist on antiretroviral therapy due to an impaired capacity for the HIV-specific T-cell response to either kill infected cells or control virus once there is viral rebound. We are exploring the role of drugs and antibodies developed for treatment of malignancy to enhance HIV-specific T-cells to kill latently infected cells. Our current major approaches include the use of immune checkpoint blockers and drugs that activate NK cells including pomalidomide.
HIV and HBV co-infection
Co-infections with viral or bacterial pathogens cause significant morbidity in patients with HIV. In the case of HIV/HBV co-infection, morbidity and mortality secondary to liver disease is greatly increased compared to those infected with HBV or HIV alone. Mortality remains elevated even after treating both the HIV and HBV virus. We are interested in the mechanisms of how HIV can accelerate liver disease in patients co-infected with HBV and why there is enhanced HBV clearance following antiviral treatment of HIV-HBV co-infection. These studies include laboratory based programs and clinical cohort studies based in Thailand, Malaysia and India. These studies could potentially lead to new treatments for liver disease and strategies for an HBV Cure.
COVID-19 natural history, diagnosis and treatment
Our lab is supporting a range of observational and interventional studies led by members of the Department of Infectious Diseases to establish a biobank for COVID-19 patients. We are also developing novel tests to diagnose SARS-CoV2, models to understand the pathogenesis of the virus and assessing the role of CRISPR-Cas 13, in collaboration with Professor Joe Trapani at the Victorian Comprehensive Cancer Centre.
- Professor Sharon Lewin, Director, The Peter Doherty Institute for Infection and Immunity; Head, Department of Infectious Diseases, Melbourne Medical School
- Dr Thomas Rasmussen, Associate Clinical Director of HIV Cure Studies
- Ajantha Rhodes, Clinical Operations Manager & Laboratory Manager; Head, Virology Core
- Dr Judy Chang, Research Systems Administrator – Clinical Research; Head, Immunology Core
- Dr Jennifer Audsley, Post-doctoral Research Fellow
- Dr Jori Symons, Postdoctoral Research Fellow
- Dr Jennifer Zerbato, Postdoctoral Research Fellow
- Dr Wei Zhao, Postdoctoral Research Fellow
- Dr Chris Chiu, Postdoctoral Research Fellow
- Dr Celine Gubser, Postdoctoral Research Fellow
- Dr Kasha Singh (Clinician Researcher)
- Dr Matthew Pitman (Clinician Researcher)
- Ms Zuwena Richardson
- Ms Rachel Pascoe
- Ms Paula Cevaal
- Mr Haoming Liu
- Mr Jared Stern
- Mr Abdalla Ali
- Carolin Tumpach, Research Support Officer; High Containment Laboratory Manager; Chromium 10X Conroller Platform Manager
- Rosalyn Cao, Research Support Officer
- Danielle Fong, Research Support Officer
Research Support Staff
- Dr Jasminka Sterjovski (Research Manager)
- Barb Scher (Clinical Trials Liaison Officer)
- Associate Professor Joe Sasadeusz
- Associate Professor Edwina Wright
- Dr James McMahon
- Dr Jill Lau
- Addressing the major challenges in HIV vaccine and cure research
Kent S, Lewin SR, Cooper DA, Caruso F, Palmer S, Kelleher A, Davenport M.
CIBNHMRC Program Grant APP1149990
5 years; $16,136,755
- The future of HIV care - long term remission and eliminating co-morbidities
CIANHMRC Practitioner Fellowship APP1135851
5 years; $577,188
- Delaney AIDS Research Enterprise (DARE) to find a cure.
Deeks S, Picker L, Lewin SR, McCune M
Co-investigatorNational Institutes for Health UM1AI126611
5 years; $3million USD
- Australian Partnership (for) Preparedness Research on InfectiouS (Disease) Emergencies (APPRISE)
Lewin SR, Sorrell T, McVernon J, Webb S, Kaldor J, Andrews R, Cheng A, Gilbert G, Smith D, Alexandersen S
CIANHMRC Centres of Research Excellence
5 years; $4,996,416
- Therapeutic targeting of SARS-CoV-2 RNA with CRISPR-Cas13
Lewin SR, Chen Z, Trapani J, Fareh M, Vincan E, Zhao W.
CIASino-Australia COVID-19 Partnership Seed Funding
1 year; $50,000
- Developing and Implementing an Ethical Framework for HIV Phylogenetic Analysis In Australia
Lewin SR, Williamson D, Wright E, Fairley C, Hocking J, Ward J, Keogh L, Crouch S, Alpren C
CIANHMRC Partnership Grant (APP1198800)
4 years; $537,855
- Evaluating direct and indirect effects of SARS-CoV-2 on multiple organ systems using stem cell-derived human tissues
Little M (CIA)… Lewin SR
Co-IMedical Research Future Fund (MRFF)
- COVID-19 Strategic Planning and Delivery of Testing
Lewin SR, Howden B, Stinear T, Williamson D, Catton M, Monk I, Guerillot R, Lee J, Sherry N, Bond K.
CIAMedical Research Future Fund (MRFF)
1 year; $2,699,278
- A hidden reservoir? An in-depth analysis of HIV integration across the entire human genome
Lewin SR, Cameron D, Symons J, Chopra A
CIAAmerican Foundation for AIDS Research (amfAR)
- Triplex forming oligonucleotides: Block and Lock as a strategy for HIV cure
Symons J, Lewin SR, Caruso F.
CIBMelbourne HIV Cure Consortium Small Grant Scheme
1 year; $20,000
- Effects of Leidos peptides (LD01/LD10da/LD16a) on HIV latency and HIV-specific T-cell function
Lewin SR, Rasmussen TA
2 years; $235,270 AUD
- Safety and immunogenicity of early or deferred single low dose nivolumab (0.3mg/kg) with an HIV DNA/MVA vaccine in HIV‐infected adults on antiretroviral therapy
Melbourne HIV Cure Consortium Large Clinical Grant Scheme
2 years; $449,295
- Effect of Immune Checkpoint Inhibitors on HIV Persistence: An observational study among HIV patients with cancer
Rasmussen T, Lewin SR, Polizzotto M.
CIBMelbourne HIV Cure Consortium Small Grant Scheme
1 year; $20,000
- Defining apoptosis proteins with mass CyTOF following HIV latency reversal
Anderson J, Teh C, Zerbato J, Lewin SR
CIDMelbourne HIV Cure Consortium Small Grant Scheme
1 year; $20,000
- Mechanisms of HIV disease limitation and cure revealed in paediatric infection
Goulder P, Lewin SR, Frater J, Ndungu, T
5 years; 2.9million GBP
Selected publications from the last 5 years (total of 329 publications):
- Rasmussen TA, …. Lewin SR*. The effect of antiretroviral intensification with dolutegravir: a randomised, placebo-controlled, double-blind trial. Lancet HIV, 2018; 5(5): e221-e230 (doi: 10.1016/S2352-3018(18)30040-7).
- Fromentin R….Lewin SR…Chomont N . PD-1 blockade potentiates HIV latency reversal ex vivo in CD4(+) T cells from ART-suppressed individuals. Nature communications 2019; 10:814.
- Van der Sluis R….Lewin SR. Combination immune checkpoint blockade to reverse HIV latency. J Immunol 2020.
- Van der Sluis RM……Lewin SR*, Cameron PU*. Diverse effects of interferon alpha on the establishment and reversal of HIV latency. PLoS Pathog. 2020 Feb 28;16(2):e1008151. doi: 10.1371/journal.ppat.1008151 (* joint senior author).
- Rasmussen TA….. Lewin SR: Impact of anti-PD-1 and anti-CTLA-4 on the HIV reservoir in people living with HIV with cancer on antiretroviral therapy: The AIDS Malignancy Consortium-095 study. CID 2020 (in press).
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