25 years of trailblazing HIV/AIDS research
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 arrival of this new, more optimistic period was in part made possible by the vital work led by clinical researchers at St Mary’s Hospital from the outset of the HIV/AIDS epidemic. From the early 1980s, the hospital became the site of groundbreaking trials which would change the course of treatment and research for years to come. These included a pioneering cohort study of 400 gay men, led by the Faculty’s current Dean, Professor Jonathan Weber, who was then working as a junior doctor. Later, Professor Weber and Imperial colleagues also contributed to the influential MRC-led Delta study, which paved the way for the use of combination therapy by demonstrating that two anti-HIV drugs could prolong life and delay disease progression.
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.
Supporting sex workers through groundbreaking interdisciplinary research
Professor Helen Ward
In 1984, US researcher Dr Robert Gallo first isolated the human immunodeficiency virus (HIV) or, as it was then known, HTLV-III – the virus that causes AIDS. By the year’s end, as the epidemic gained pace, 108 AIDS cases and 46 deaths had been recorded in the UK.
At the same time, Professor Helen Ward was working as a junior doctor at the Praed Street Clinic in Paddington, west London. A colleague asked her if she would consider taking on some early-stage research into the possible risks of HIV and AIDS in sex workers, which she agreed to do “for a little while”. Soon after, however, she met Professor Sophie Day, an anthropologist following a similar line of enquiry. This marked the beginning of a groundbreaking, career-long collaboration, fusing Ward’s clinical and epidemiological training with Day’s social sciences expertise.
By the time of the Faculty of Medicine’s launch in 1997, the pair had established the pioneering Praed Street Project, a clinic and support centre tailored to the needs of London’s sex workers. In addition to sexual health services, it provided access to general healthcare, legal assistance, educational support and other vital resources. It also provided the basis for a cutting-edge, interdisciplinary research programme into HIV and other sexually transmitted infections (STIs).
“The close link between research and developing services to meet needs identified in that research is an approach we have tried to pursue ever since as an exemplar of translational research,” explains Professor Ward.
Through the Praed Street Project, from the mid-1980s to 2007, Professors Ward and Day were able to recruit consenting sex workers to unique longitudinal cohort studies. Over two decades, their research findings dismantled heavily biased perceptions of sex workers and their attitudes to sexual risk, particularly within the context of the HIV/AIDS epidemic. As well as providing vital evidence of HIV’s indirect relationship to sex work, the research revealed a nuanced picture of the many barriers and risks faced by sex workers, often absent from contemporary research, policy and opinion. Through following occupational histories of women in the study they showed how sex work was used by some to support the development of other careers, others suffered serious health issues associated with overt violence and widespread discrimination.
The Faculty has always aimed not only to deliver excellent research, but to translate that into the local population and beyond
In the late nineties, Professors Ward and Day led the European Network for HIV/STD Prevention in Prostitution, which became a vital means of sharing research and pioneering practice frameworks developed at Praed Street with collaborators across Europe.
Continuing their interdisciplinary partnership, Professors Ward and Day also led novel explorations into the role of sexual networks in the transmission of HIV and other STIs, combining epidemiological approaches with social and observational research methods.
“There's no point in just describing the evolution of a bacterium in a population, you have to understand the context in which that transmission occurs," explains Professor Ward.
“We succeeded in showing that you have to use different methods to understand these things properly.”
The pair went on to co-found Imperial’s Patient Experience Research Centre (PERC) in 2011 with funding from the NIHR Imperial Biomedical Research Centre, bringing together a multidisciplinary team of clinicians, public health specialists and social scientists. Building on the unique partnership that began in Praed Street, the Centre continues to provide vital support for scientists and clinicians seeking to shape and translate their research and services in the most effective way possible.
“The Faculty has always aimed not only to deliver excellent research, but to translate that into the local population and beyond,” says Professor Ward.
“There’s a huge amount of social knowledge you need to have in order to do this – understanding inequalities, how people live, how they access healthcare.
“Just as we found in our early research with sex workers and HIV, it’s about talking to people – it’s about observing, understanding and researching how people engage with one another.”
Portrait photo of Professor Helen Ward by Danny Fitzpatrick / Imperial College London. Photo of Professors Helen Ward and Sophie Day by Jo Mieszkowski / Imperial College London.
Pioneering national guidelines for managing HIV in pregnancy
Professor Graham Taylor
Graham Taylor, Professor of Human Retrovirology at Imperial’s Department of Infectious Disease, joined the College in 1992 as a clinical research fellow. Soon after his arrival at St Mary’s, he helped to establish a clinic for adult HIV patients within the hospital’s paediatrics department.
“The plan was to provide this one-stop appointment system, so mothers, fathers, and children with HIV could be seen at the same time, and they’d only need to come once. We wanted to eliminate unnecessary barriers to accessing care,” he explains.
“Some of the women we were treating in our family clinic became pregnant again. We decided we also needed to set up an antenatal HIV clinic, to ensure our patients were getting the best possible standard of care and to help our team develop knowledge of managing HIV infection in pregnancy.”
A research breakthrough in the mid-1990s demonstrated that the combined use of the early anti-HIV drug zidovudine and pre-labour caesarean sections could reduce mother-to-child transmission to almost zero.
“It was a fantastic advance, and that was the beginning really of being able to reduce and prevent mother-to-child transmission of HIV,” recalls Professor Taylor.
However, with the development of new anti-HIV therapies and approaches to treatment came new clinical questions: how would the drugs work in pregnant patients? Did they pose different risks and/or benefits to expectant mothers and their babies?
Elsewhere at St Mary’s Hospital, Professor Taylor had been supporting the Delta study which, in 1996, led to a significant breakthrough. Rather than using a single drug (monotherapy), combining two anti-HIV therapies (dual therapy) could prolong life and delay disease progression.
Following the advent of dual therapy, in 1998, Professor Taylor and colleagues led a small study looking at its effects in pregnant women.
“With dual therapy, we saw viral loads dropping and staying lower compared to monotherapy. However, we quickly saw the emergence of HIV resistance, especially to the drug lamivudine.
"As triple therapy was rolled out in the wider adult population, we were quick to follow suit. In just a few years, we had gone from using no drugs in pregnant women to one drug, to two drugs, to three.”
With the adoption of triple therapy, Professor Taylor worked with Dr Hermione Lyall – now a Professor of Practice at Imperial – and colleagues across London to develop the first set of national guidelines for prescribing antiretroviral therapy (ART) in pregnancy.
In just a few years, we had gone from using no drugs in pregnant women to one drug, to two drugs, to three.
First published in 1999 and adopted by the British HIV Association, the guidelines have been regularly revised to reflect and inform updates in clinical practice and research and continue to be a vital resource for healthcare professionals today.
Professor Taylor has continued to lead research into dosing anti-HIV drugs for pregnant women, as well as understanding their relationship to pre-eclampsia and pre-term birth, working with colleagues in the March of Dimes, European Prematurity Research Centre in the Institute of Reproductive Developmental Biology (IRDB). He also leads the St Mary’s arm of PANNA, a European study examining and comparing how new anti-HIV drugs work in pregnant and non-pregnant HIV-infected women.
Photos by Thomas Angus / Imperial College London
Changing the course of Zimbabwe’s HIV epidemic
Professor Simon Gregson
For over three decades, Simon Gregson – Professor in Demography and Behavioural Science and Director of the Manicaland Centre for Public Health Research – has been at the forefront of HIV research in sub-Saharan Africa. In early-1990s rural Zimbabwe, Professor Gregson and colleagues from Imperial and the Biomedical Research and Training Institute (BRTI) pioneered one of the first HIV cohort studies in Africa, despite significant social barriers and economic instability.
Honde Valley, Mutasa District, Manicaland (1994)
Honde Valley, Mutasa District, Manicaland (1994)
“In the early days, there was a lot of denial – particularly around the connection between HIV and AIDS,” he recalls.
“People were dying, but in many ways, their deaths weren’t visible.
“We weren't allowed to do HIV testing in the community. We had to rely on collecting dried blood from pregnant women in antenatal clinics and people attending STD services, which we could use to perform tests. We also spent a lot of time measuring mortality rates in a two-round household census and by reviewing death registration records.”
People were dying, but in many ways, their deaths weren’t visible.
Despite the challenges faced by Professor Gregson and his colleagues, the team’s early-stage work would prove vital in influencing major HIV policy changes in Zimbabwe and thereafter changing the course of the epidemic. It would also provide the groundwork for the formation of the Manicaland Centre, based at BRTI, which continues to carry out multidisciplinary research into the spread, impact and control of HIV.
“We could see clear evidence that death rates were increasing,” he explains.
The report produced by the team, detailing the findings of their pilot study, was the first evidence of excess mortality due to AIDS in the country. This was demonstrated, in part, by comparing patterns of death rates by sex and age group with mathematical model projections of what would be expected 5-15 years into a major epidemic. These vital projections were created using a model developed by Professor Geoff Garnett, Professor Sir Roy Anderson and others based at Imperial.
Mutarazi Falls, Honde Valley, Mutasa District, Manicaland
Mutarazi Falls, Honde Valley, Mutasa District, Manicaland
“Our research was picked up by policymakers and key decision-makers, and it ended up informing the government’s decision to establish the National AIDS Council in Zimbabwe along with a National AIDS Trust Fund, supported by a new tax.”
The rollout of these bold new initiatives, backed by the pioneering research of Professor Gregson and his colleagues, was ultimately a key factor in the subsequent decline of new HIV cases in the region.
But the pilot study led by the Manicaland team would go on to have an impact far beyond these early policy shifts. With new funding from Wellcome and the Bill and Melinda Gates Foundation, Professor Gregson, his long-term collaborator Dr Constance Nyamukapa and their colleagues were able to further develop and continue their unique research programme.
Spanning from 1998 to 2013, the Manicaland General Population Cohort study ran across 12 sites in east Zimbabwe to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour and the demographic impact of HIV at a population level.
Study interview in progress
Study interview in progress
The cohort quickly became a valuable resource for fellow HIV researchers, providing essential data to underpin a wide range of projects.
In 2006, the Manicaland cohort provided the first evidence for declines in HIV prevalence in Zimbabwe associated with reductions in sexual risk behaviours. The data from the cohort was then used in subsequent studies to assess the effectiveness of national HIV prevention programmes focused on reducing new HIV infections and AIDS deaths and in improving the wellbeing of orphaned children.
The cohort has also supported several studies investigating the role of social capital in HIV control in Zimbabwe, including a 2011 paper which revealed strong evidence of associations between female participation in a range of local community groups and reductions in HIV risk.
Community group (burial society) in the Honde Valley, Mutasa District (2002)
Community group (burial society) in the Honde Valley, Mutasa District (2002)
“We found that women who were well-connected in their communities, and who actively participated in these different groups, tended to be among the first people to take up new HIV services,” says Professor Gregson.
The research was significant in highlighting the importance of community leadership and participation as key factors in the success of HIV control interventions.
Today, the Manicaland Centre team maintains a far-reaching research portfolio, which includes several projects investigating different aspects of HIV testing, prevention and policy. The Centre also continues to work in close partnership with Imperial modelling and epidemiology experts, including Professor Tim Hallett and researchers based within the Department of Infectious Disease Epidemiology.
The Manicaland team pictured in 2017. Pictured are Imperial's Professor Simon Gregson (top row, far right), Professor Tim Hallett (top row, far left) and Dr Constance Nyamukapa (bottom row, far right)
The Manicaland team pictured in 2017. Pictured are Imperial's Professor Simon Gregson (top row, far right), Professor Tim Hallett (top row, far left) and Dr Constance Nyamukapa (bottom row, far right)
Photos provided courtesy of Professors Simon Gregson and Tim Hallett
Tackling HIV at a population level and searching for a cure
Professor Sarah Fidler
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.
As the medications became safer, Professor Fidler decided to investigate the best strategy for their use. She co-led the international SPARTAC trial from 2003-07. This study tested whether a short course of antiretroviral therapy (ART) – if given close to the time of new HIV infection – could lead to a delay in the immune damage usually caused by HIV. The Wellcome-funded trial recruited 366 adults from across Australia, Brazil, Ireland, Italy, South Africa, Spain, Uganda and the UK.
SPARTAC’s findings definitively demonstrated that a short course of ART taken in the early stages of HIV infection slowed damage to the immune system and delayed the need for long-term treatment.
“Since we knew that treatment – particularly in the early stages – was much more effective than no treatment at all, we started looking at designing strategic studies to understand in more detail how best to use it,” explains Professor Fidler.
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.
We wanted to see whether, in settings with a high prevalence of HIV, it was possible to reduce incidence at a population level
Spanning 21 communities and one million residents, the PopART trial demonstrated that a community-wide test and treat approach reduced the number of new HIV infections by approximately 20%.
“We wanted to see whether, in settings with a high prevalence of HIV, it was possible to reduce incidence at a population level by really encouraging everyone within a community to test for HIV, and then immediately starting treatment for those who’ve tested positive.”
Professor Sarah Fidler
Professor Sarah Fidler
Significantly, the trial found that, in communities where this strategy was implemented, new HIV infections were reduced by 30% compared to communities receiving standard care. Since their publication in 2019, PopART’s findings have been incorporated into WHO guidelines on HIV testing and strategy.
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.
From 2015-18, she led the RIVER trial, which tested an experimental approach known as ‘kick and kill’, designed to ‘wake up’ hidden reservoirs of HIV in the body in order to eradicate it. The trial ultimately found that there was no difference between patients receiving this new approach to treatment versus standard care. However, it has offered an important stepping-stone for further research in this area.
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.
Photos by Kim Cloete, Zambart and Thomas Angus / Imperial College London
Shaping policy to increase antiretroviral therapy uptake on a global scale
Professor Tim Hallett
Throughout his career at Imperial, Professor Tim Hallett has led vital work into the epidemiology of HIV and understanding the large-scale impact of intervention and prevention strategies.
In 2010, he founded the HIV Modelling Consortium at Imperial – with the secretariat based at UCL since 2019 – to bring together a diverse network of epidemiologists, modellers, health economists and other key stakeholders in the fields of HIV research and policy.
"At the time, the modelling work was saying different things. That’s why I founded the consortium – to speak with one voice to policymakers,” he explains.
Since its launch, the consortium has provided essential evidence and data to policymakers to inform the design of effective HIV programmes around the world.
From 2012-16, Professor Hallett and colleagues at Imperial developed model-based estimates to help answer two essential questions: When should you start antiretroviral therapy (ART), and what is the best way of monitoring patients who are undergoing treatment?
Before this time, treatment for HIV with ART had been restricted to patients with the most advanced disease. During treatment, a patient’s condition would be monitored using a CD4 cell count, which indicates how well the immune system is working.
However, policymakers had been faced with conflicting evidence around the clinical benefits and costs of starting treatment earlier, and monitoring patients by looking at their viral load (the amount of HIV in the blood).
I founded the consortium to speak with one voice to policymakers
Working with members of the consortium over a period of three years, Professor Hallett’s team produced population-level evaluations of the policy changes, demonstrating both their public health impact and cost-effectiveness in different settings.
The team's findings were instrumental in the revision of the World Health Organization (WHO)’s guidelines on the use of ART to treat and prevent HIV infection in 2013. The recommendations included a new threshold for starting ART, laying the foundation for earlier initiation of treatment.
Additional work by Professor Hallett’s team then informed a second revision to WHO guidelines in 2016, which recommended a universal treatment approach for all HIV-positive persons – regardless of their CD4 count.
The updated WHO recommendations prompted wider changes to national guidelines for treating HIV. This, in turn, led to a substantial increase in the uptake of ART in low- and middle-income settings from an estimated 13 million in 2013 to 26 million in 2020.
In addition, the evidence provided by Professor Hallett and colleagues on the clinical benefits and cost-effectiveness of viral load testing has helped to support its widespread adoption across low-income settings.
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