RIO’s Prof Sarah Fidler featured in a news piece celebrating 25 years of Imperial’s Faculty of Medicine and trailblazing HIV and AIDS research
1st Dec 2022 by Genevieve Timmins, Imperial College London
The launch of Imperial’s Faculty of Medicine in 1997 coincided with a new era in HIV/AIDS treatment and research. Just prior to its creation came the groundbreaking revelation that combining three antiretroviral drugs could drastically improve the prognosis of people living with HIV. The subsequent rollout of triple therapy in the UK quickly led to a steep decline in the number of people developing and dying from AIDS.
The creation of a new Faculty of Medicine in 1997 represented a unique opportunity to build on this established culture of trailblazing HIV/AIDS research, while ushering in a new wave of talent and ideas. As the Faculty celebrates its Silver Jubilee, we reflect on the groundbreaking contributions of five leading HIV researchers and their teams over the past 25 years, and their wider historical and social contexts.
In the mid-1990s, Sarah Fidler – Professor of HIV and Communicable Diseases – was embarking on her PhD at St Mary’s Hospital.
“At the time, we only had early-stage treatments for HIV, which didn’t work very well. The medicines we had available for people living with HIV had a lot of side effects, which meant that people were advised to delay starting treatment until their immune systems weren’t working very well,” she recalls.
Following the discovery that ART enhanced individual survival while also protecting against the risk of passing HIV on to partners and infants, Professor Fidler began co-chairing a new project with international colleagues and funders: the groundbreaking PopART trial. Its focus was on exploring how to implement an acceptable and effective approach to delivering community-wide HIV testing and treatment in a cluster randomized controlled trial in Zambia and South Africa.
In parallel to this work, Professor Fidler has been leading work into new treatments for HIV and – with the support of the NIHR Imperial BRC-funded CHERUB collaboration – possible cures.
One example of this is the ongoing RIO clinical trial, jointly led by Professor Fidler and scientists at the University of Oxford and the Rockefeller University. The trial will test whether a new type of therapy called broadly neutralising monoclonal antibodies (or bNAbs) can keep HIV under control without daily antiretroviral treatment (ART) tablets.
Professor Sarah Fidler on BBC’s Newsnight programme
On Monday, 4th July 2022, Professor Sarah Fidler was interviewed on the BBC’s Newsnight programme last night together with the CEO of the Terrence Higgins Trust, Ian Green. It has been 40 years since the death of Terrence Higgins who was the first person in the UK to die of an AIDS-related illness.
The interview covered important issues such as testing, knowing your status, the reliability and efficacy of current HIV treatment, how to overcome stigma, community participation, and what future treatments might look like.
Please view the interview here (from 27mins – requires a BBC login).
10th June 2022: Listen to the latest Shot & Chaser podcast with our RIO Trial Chief Investigator, Professor Sarah Fidler, where she discusses the RIO Trial in the context of cure.
Please follow this link to the podcast.
Meeting Report Hybrid Symposium 2021
Last October experts in the field of infectious disease came together in a hybrid scientific meeting. It took place online and attracted over 150 participants from over a 12 different countries. The meeting address recent insights in two viral infections, HIV and SARS-COV-2.
The meeting report is now available. It is also still possible to rewatch the 2021 Hybrid Symposium.
Research Priorities for an HIV Cure: IAS Global Scientific Strategy 2021
CHERUB Investigator Professor Sarah Fidler and Patient Representative Simon Collins & advocate at HIV i-Base have co-authored the third edition of Research Priorities for an HIV Cure: IAS Global Scientific Strategy 2021.
This edition was published on World AIDS Day 2021 in Nature Medicine. It highlights critical gaps, progress made, and the next steps science must follow towards a scalable, affordable and globally accessible cure.
Yet, one question remains: how close are we to an HIV cure? In this special World AIDS Day episode of HIV unmuted, the IAS podcast the human endeavours behind the journey and the hope it would bring to 38 million people living with HIV are shared.
BBC News: Rare case of woman's body ridding itself of HIV
A woman from Argentina appears to have rid herself of HIV without drugs or treatment in the second documented case of its kind in the world.
CHERUB Investigators Prof Sarah Fidler and Prof John Frater interviewed.
16 November 2021
A woman from Argentina appears to have rid herself of HIV without drugs or treatment – the second documented case of its kind in the world.
Doctors believe the patient’s immune system cleared the virus on its own.
Tests on more than a billion of her cells found no viable trace of the infection, Archives of Internal Medicine reports.
If this process could be harnessed, it might offer a way to wipe out or effectively cure HIV, experts say.
[…]
‘Abortive infection’
Prof John Frater, from the University of Oxford, told BBC News while it was almost impossible to say if someone had been truly cured of HIV, the investigators had done “as much as could be asked of them with current technology” to prove it.
“The key question is whether this patient has actually cured themselves or, alternatively, had some form of abortive infection, which tried to get going but the embers were snuffed out early,” he said.
“Her immune system clearly shows a memory of having been infected, so there seems to be no question that she was.
“Regardless, there may be similar patients out there, offering much to learn in the search for a HIV cure.”
Prof Sarah Fidler, an expert in HIV medicine at Imperial College London, said the work would help inform immune therapies currently under development.
RIO trial represented at EACS 2021
The 18th European AIDS Conference (EACS) took place on the 27th – 30th of October 2021 both in London and online
From the RIO study team, Professors Sarah Fidler, Marina Caskey and John Frater and our Patient Representative Mr Simon Collins were part of the scientific programme of the conference.
Prof Fidler chaired a session titled HIV cure: What do we need to advance?
Prof Caskey participated in a panel discussion for the above session HIV cure: What do we need to advance? and was invited to give a presentation titled Application of the monoclonal broadly neutralizing antibodies: From vaccine to HIV cure research.
Prof Frater co-chaired a session titled ANRS “HIV Cure” session Immunotherapies: How to enhance the “kill”.
Mr Collins took part in a panel discussion titled HIV-related mortality: How to measure it and prevent it, and also was one of the winners of the biennial EACS Award.
For the official highlights from the event please visit the NAM aidsmap website.
RIO Patient Representative, Mr Simon Collins, wins biennial EACS Award
Simon Collins was the joint award winner at the 18th European AIDS Conference held on the 27th – 30th October 2021.
“The [opening] ceremony ended with the presentation of the biennial EACS Award in recognition of an individual’s longstanding, impactful and sustained professional contribution to the field of HIV. In 2021 a joint award was made to two people who have both made significant but different contributions to the HIV sector.”
[…]
“The second joint award winner is Simon Collins, an outstanding long term UK based HIV advocate and activist who combines championing the rights of people living with HIV with a commitment to sharing knowledge and science in the community through the HIV i-Base Treatment Bulletin and help line.”
First major study of new HIV therapy opens to recruitment
by Geneviéve Timmins
01 July 2021
The RIO clinical trial will test whether a new type of therapy can keep HIV under control without daily antiretroviral treatment (ART) tablets.
The novel therapy uses a combination of two experimental antibodies (called broadly neutralising monoclonal antibodies, or bNAbs) which have been designed by scientists at the Rockefeller University to target multiple strains of HIV.
The RIO study, jointly led by Imperial College London, the University of Oxford and the Rockefeller University, will use viral load blood tests to measure how long HIV can be controlled using bNAbs. To do this, trial participants will be randomised to receive either a bNAb injection or a placebo before stopping their ART tablets.
Currently, people living with HIV take a daily tablet of ART, which keeps the virus at undetectable levels, making it untransmittable. RIO is looking at whether this new approach might allow people living with HIV to have periods of time where they do not need to take daily ART. Participants will be asked to restart their ART when the virus becomes detectable in a blood test (‘viral rebound’).
The study will also test the mechanisms by which these experimental antibodies work. Scientists will measure whether the immune system is boosted by the bNAbs, resulting in continued control of HIV, even after the antibodies have cleared.
A new approach to HIV treatment
RIO Chief Investigator, Professor Sarah Fidler of Imperial’s Department of Infectious Disease, said: “We are really pleased to open the RIO trial, the first randomised trial of its kind, designed to carefully measure the effects of the new treatments to control HIV after stopping ART.”
Professor John Frater, University of Oxford, who is co-lead of the study said: “The RIO trial is the first major study to test an exciting new class of treatments for HIV, with potential to allow people to stop taking tablets and even to confer a form of remission from infection – a crucial pathway in the search for an HIV cure.”
"The new treatments might let some people living with HIV stop ART for six months or longer - and still keep viral load undetectable," adds Simon Collins, an advocate at HIV i-Base.
“This study provides a unique opportunity to evaluate the effects of antibodies on the participants’ own immune responses against HIV. The participants in this study are people living with HIV who started treatment early after infection who we think have stronger immune responses to fight off the virus when ART is discontinued”, said Marina Caskey, Co-Investigator at the Rockefeller University.
Trial launch
Following initial delays to the trial due to the COVID-19 pandemic, RIO is now open to recruitment with extra precautions to ensure the safety of the participants. Individuals joining the trial will be tested for COVID-19 and will have received their COVID-19 vaccination.
The study aims to recruit 72 participants and will run until July 2024.
Seven centres are participating in RIO:
St Mary's Hospital, London, Imperial College Healthcare NHS Trust,
Royal Free Hospital, Royal Free London NHS Foundation Trust,
Mortimer Market Centre, Central and Northwest London NHS Foundation Trust,
Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust,
St Thomas’ Hospital, London, Guy's and St Thomas' NHS Foundation Trust,
The Royal London Hospital, Barts’ Health NHS Trust,
The Royal Sussex County Hospital, Brighton and Sussex University Hospitals NHS Trust.
The University of Oxford and the Rockefeller University in New York will both study samples from the participants to work out how the new antibodies are working, and how the immune system is responding.
The RIO trial is funded by the Bill & Melinda Gates Foundation and sponsored by Imperial College London. The trial is jointly coordinated by Imperial College London, the University of Oxford and the Rockefeller University.
RIO is part of the CHERUB research collaboration. CHERUB (‘Collaborative HIV Eradication of Reservoirs UK BRC’) is a UK network of internationally recognised doctors and investigators from the NIHR Biomedical Research Centres in London, Oxford and Cambridge, working together with patients and community representatives to find a cure for HIV infection.
For more information on RIO, please visit the trial website.
Read original press release
Universal ‘Test and Treat’ for HIV cost-effective in high prevalence regions.
12 March 2021
Rolling out home-based testing and universal treatment for HIV is cost-effective and can cut the incidence of cases in high-prevalence communities.
These are the findings of a major HIV-prevention study involving more than one million people in Zambia and South Africa, published in The Lancet Global Health.
IAS bids sad farewell to Timothy Ray Brown, the “Berlin patient”
30 June 2020
It is with a profoundly heavy heart that IAS – the International AIDS Society – today mourns the passing of Timothy Ray Brown, the first person to be cured of HIV.
Known as the “Berlin Patient”, Mr Brown was cured of HIV in 2008 after undergoing a complex stem cell transplant for acute leukaemia.
For the past six months, Mr Brown had been living with a recurrence of the leukaemia that had entered his spine and brain. He had remained HIV free.
“On behalf of all its members and the Governing Council, the IAS sends its condolences to Timothy’s partner, Tim, and his family and friends,” Adeeba Kamarulzaman, President of the IAS and Professor of Medicine and Infectious Diseases at the University of Malaya, said.
“We owe Timothy and his doctor, Gero Hütter, a great deal of gratitude for opening the door for scientists to explore the concept that a cure for HIV is possible.
Mr Brown, living with HIV and with acute myeloid leukaemia, received a bone marrow transplant in Berlin, Germany, in 2007. The donor was naturally resistant to HIV infection because of a mutation in the CCR5 gene, a critical protein required by HIV to enter and infect cells.
Mr Brown stopped antiretroviral therapy (ART) very soon after the transplant and he remained free of any detectable virus. In other words, he was cured. His experience suggested that HIV might one day be curable. This fuelled a range of efforts by researchers and institutions focusing on HIV cure research.
One such effort is the IAS Towards an HIV Cure initiative, established in 2011 to promote and facilitate the search for a safe and affordable cure that can be scaled up. Professor Sharon Lewin, President-Elect of the IAS and Director of the Doherty Institute in Melbourne, Australia, co-chairs this IAS initiative with Mark Dybul, a former Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria and US Global AIDS Coordinator. Steven Deeks, Professor of Medicine in Residence at the University of California is the Chief Scientific Advisor of the Towards an HIV Cure Advisory Board.
A full decade after Timothy Brown’s cure, Adam Castillejo, who had also been living with HIV, reportedly remained in HIV remission off ART, 19 months after receiving a bone marrow transplant for Hodgkin’s lymphoma from a CCR5-negative donor. Now known as the “London Patient”, he remains in remission and is widely considered to be the second man cured of HIV.
“Although the cases of Timothy and Adam are not a viable large-scale strategy for a cure, they do represent a critical moment in the search for an HIV cure,” Sharon Lewin said.
“Timothy was a champion and advocate for keeping an HIV cure on the political and scientific agenda. It is the hope of the scientific community that one day we can honour his legacy with a safe, cost-effective and widely accessible strategy to achieve HIV remission and cure using gene editing or techniques that boost immune control.”
In late August, it was reported that Loreen Willenberg, a woman who had been living with HIV since 1992, had no traces of intact HIV despite not using ART. She may be the first person cured of HIV without undergoing a risky bone marrow transplant. Researchers believe that she may be an “extreme elite controller”, where only fragments of HIV remain and these fragments are unable to replicate.
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The London patient: long-term follow-up suggests no detectable HIV virus
Making a Difference
Long-term follow-up of the ‘London patient’, the second patient to ever achieve sustained HIV remission after ceasing antiretroviral treatment, has suggested that there is no active detectable HIV virus remaining.
Second person ever to be cleared of HIV reveals identity.
The second person ever to be cleared of HIV has revealed his identity, saying he wants to be an “ambassador of hope” to others with the condition.