Collaborative HIV Eradication of viral Reservoirs: UK BRC Scientific Workshop 4 th December 2015
We are delighted to welcome you to our 5th annual CHERUB Science Day. CHERUB is Collaborative HIV Eradication of Viral Reservoirs: UK BRC. CHERUB was one of the first cooperatives of the five UK Biomedical Research Centres (Oxford, Cambridge, Imperial, UCL and King s) and provides a platform in the UK to engage in research towards finding a cure for HIV infection. Members of CHERUB include clinicians undertaking clinical trials of new interventions designed to impact the HIV reservoir, basic scientists exploring novel approaches to measuring, imaging and targeting the reservoir, and people living with HIV and patient advocates helping to shape strategy for HIV Cure research. We have a busy and exciting agenda, and we hope that the meeting stimulates some excellent discussion. With our best wishes, and thanks again for joining us today. Sarah Fidler John Frater On behalf of the CHERUB Steering Committee and Programme Liaison Group
CHERUB Collaboration CHERUB Scientific Steering Committee Chair: Jonathan Weber Abdel Babiker Sarah Fidler John Frater Ravindra Gupta Andrew Lever Mike Malim Julie Fox CHERUB Programme Liaison Group Lucy Dorrell Caroline Foster Mark Wills Axel Fun Jodi Meyerowitz Eleni Nastouli Matthew Pace Kholoud Porter CHERUB Secretariat CHERUB Patient Advocates Hanna Box Cherry Kingsley Simon Collins Damian Kelly Lisa Thorley Our Vision To involve patients and researchers in advancing the HIV Cure agenda To enhance partnerships between healthcare providers and universities To develop a national initiative towards a cure for HIV To establish a Centre of Excellence for HIV Cure Research To foster local and international partnerships To encourage and support junior researchers
Our Studies The first RCT to explore kick & kill in primary infection, using the HDACi vorinostat with the HIVcons vaccine. Funded by an MRC DCS award of 1.9 million. Recruitment opens Q4 2015 Autologous virus VLP constructs made by cloning the exact viral sequence of a patient will be used to pulse patients own dendritic cells (DC), to see if such an autologous vaccine is capable of recognising and eliminating HIV from latently infected cells. A platform of work exploring the HIV reservoir in primary infection. N=245 participants at three London centers. Currently supported through the Oxford Martin School and the MRC. Prospective HIV Chemotherapy Cohort Study A prospective observational study to investigate the effects on HIV reservoirs of cytotoxic chemotherapy agents in patients with HIV-associated malignancies. Fully recruited with analyses and lab assays underway reports Q4 2015 HIV-infected young people and children on suppressive ART initiated from < 1 year, to see if ART with sustained viral suppression for > 10 years will decrease the HIV reservoir. Phase 1 - Fully recruited. IVIG in Primary HIV Infection This RCT investigated whether high dosage IV immunoglobulin in ART-treated acute infection leads to a reduction of the HIV-reservoir compared with ART alone. Fully recruited; due to report Q4 15. This study explored the immunomodulatory effect of the CCR5-antagonist Maraviroc, and the impact on inflammatory markers and the reservoir in the blood and gut. Fully recruited; due to report Q4 15.
PITCH PILOT: a prospective pilot study exploring correlates of potential post treatment control amongst treated seroconverters Viiv Dolutegravir: RCT pilot of impact of Dolutegravir vs bpi on gut associated HIV reservoir HEATHER Gut Sub-study: Investigation of gut HIV reservoirs, Gut-associated lymphoid tissue immune activation and microbiome changes after years of ART amongst treated HIV seroconverters Selected Outputs from 2014-2015 Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Hurst J, Hoffmann M, Pace M, Williams JP, et al.. Nat Commun. 2015 Oct 9;6:8495 Thirty years of treating HIV-1 infection: where next? Frater J.Trans R Soc Trop Med Hyg. 2015 Apr;109(4):229-30 Advancing the HIV cure agenda: the next 5 years. Thornhill J, Fidler S, Frater J.Curr Opin Infect Dis. 2015 Feb;28(1):1-9. Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection. Thornhill J, Inshaw J, Oomeer S, et al. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19480. HIV-1 DNA predicts disease progression and post-treatment virological control. Williams JP, Hurst J, Stöhr W, et al..elife. 2014 Sep 12;3:e03821 (SELECTED AS ONE OF TOP 6 ELIFE PAPERS) Failure of daily tenofovir to prevent HIV transmission or the establishment of a significant viral reservoir despite continued antiretroviral therapy. Davies O, Alexander H, Robinson N et al.. J Int AIDS Soc. 2014 The importance of viral blips and duration of therapy initiated in primary infection in maintaining viral control after stopping cart. Fidler S, Olson A, Fox J, et al. J Int AIDS Soc. 2014 Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection. Thornhill J, Inshaw J, Oomeer S, et al. J Int AIDS Soc. 2014. Community advocate meetings UK CAB 2015 EACS Barcelona 2015 Public Engagement Cheltenham Science Festival Science Museum London International engagement IAS "Towards a Cure" symposium invited presentation of CHERUB research (Vancouver 15) Representation IAS Scientific Working group Representation ACTG Cure TSG
Location/Time CHERUB Collaborative HIV Eradication of viral Reservoirs: UK BRC Meeting Scientific Meeting Agenda No 5 Date 4/12/2015 Friday 4 th December 2015, 11:00-17:00 Solar Room, 170 Queen s Gate,, South Kensington 10:30 11:00 Registration 11:00 11:05 Welcome from Chair Jonathan Weber 11:05 11:30 CHERUB review of the year John Frater 11:30 11.45 Patient Perspectives on Cure Research Damian Kelly 11:45 12:15 Cell-to-cell spread of HIV-1: a barrier to eradication? Clare Jolly 12:15 13:15 Oral Abstracts Nos 1-4 (15 mins each 10 talk, 5 questions) Chair: Julie Fox a. Virological Remission after ART Interruption in African HIV-1 Seroconverters Morgane Gossez b. Post treatment control or treated controllers? a comparison of viral remission Genevieve Martin in treated and untreated patients with primary HIV infection c. Immune resilience and CD4/8 ratio recovery in perinatally acquired HIV-1 infection; Katrina Pollock hope for HIV Cure research? d. Preservation of long-lived memory CD4+ T cells is associated with a lack of Emily Adland disease progression in paediatric HIV-1 infection 13:15 14:00 Lunch 14:00 14:30 HIV eradication efforts: A Danish perspective Martin Tolstrup 14:30 15:30 Oral Abstracts Nos 5-8 (15 mins each 10 talk, 5 questions) Chair: Mike Malim e. Histone Deacetylase Inhibitors Enhance Susceptibility of CD4T Cells to NK Killing Matthew Pace but Inhibit NK Cell Function f. Development of Radiotracers for Imaging HIV-1 Replication Sites In Vivo Maxwell Handley g. HIV-1 exploits early cell cycle transitions in terminally differentiated macrophages Ravindra Gupta to bypass SAMHD1 restriction h. Detection of Replication Competent HIV from Latently Infected CD4+ T Cells Axel Fun 15:30 15:45 Afternoon Break 15:45 17:00 Oral Abstracts Nos 9-13 (15 mins each 10 talk, 5 questions) Chair: Lucy Dorrell i. Host determinants of HTLV-1 integration site preference Amy McCallin j. Physiological hypoxia influences the reactivation of latent integrated provirus Anurag Kulkarni in a Hif-independent fashion in PBMCs from HTLV-1 infected individuals k. A novel conserved-region T-cell mosaic vaccine with very high global coverage of Tomáš Hanke HIV-1 variants is recognized by protective responses in chronic untreated infection l. Characterising the development of Broadly Neutralising Antibodies following Luke Granger Primary HIV infection m. Detection and immune-mediated killing of primary HIV-infected resting CD4+ T cells Zoë Wallace by engineered T cell receptors 17:00 17:25 Ongoing CHERUB studies and future plans Sarah Fidler 17.25 17:30 Closing remarks Mike Malim 17:30 18:30 Drinks reception
CHERUB Workshop Attendees Emily Adland Abdel Babiker MRC Clinical Trials Unit at UCL Charles Bangham Rachel Bennett MRC Clinical Trials Unit at UCL Hanna Box John Cason Cherrelle Dacon Lucy Dorrell Tomas Doyle Royal Free Hospital NHS Trust Sarah Fidler Caroline Foster Imperial College NHS Trust Julie Fox John Frater Axel Fun Michelle Gabriel MRC Clinical Trials Unit at UCL Philip Goulder Luke Granger Morgane Goussez Ravi Gupta University College London Elizabeth Hamlyn Maxwell Handley Tomáš Hanke Jack Hirst Emily Hopkins Jacob Hurst The Institute of Cancer Research Clare Jolly University College London Damian Kelly Community Representative Cherry Kingsley Sabine Kinloch Royal Free Hospital NHS Trust Nigel Klein Great Ormond Street Hospital Kristen Kuldanek Anurag Kulkarni Thomas Lehner Andrew Lever Mike Malim Genevieve Martin Amy McCallin Katie McFaul Dean Street Clinic Jodi Meyerowitz Hoi Ping Mok Eleni Nastouli University College London Nicholas Norton Nneka Nwokolo Chelsea and Westminster Hospital Matthew Pace Sarah Pett MRC Clinical Trials Unit at UCL Prabhjeet Phalora Chan Phetsouphanh Katrina Pollock Frank Post Hannah Roberts Quentin Sattentau Jonathan Stoye The Francis Crick Institute Lisa Thorley UK CAB John Thornhill Martin Tolstrup Aarhus University Hospital, Denmark Zoë Wallace Jonathan Weber Mark Wills Xiao-Ning Xu
Funders Linked Studies Prospective HIV Chemotherapy Cohort Study IVIG in Primary HIV Infection