Continued follow-up of the United Kingdom Collaborative HIV Cohort (UK CHIC) and the UK HIV Drug Resistance Database (UK HDRD), 2014-2019

Lead Research Organisation: University College London
Department Name: Infection and Population Health

Abstract

The number of people living with the human immunodeficiency virus (HIV) in the UK continues to increase. Current treatment for HIV is very effective and, as a result, the life expectancy of a person living with HIV has increased substantially over the past 15 years. However, HIV remains extremely costly to the National Health Service and there are still many challenges that must be faced to ensure that people with HIV continue to live full and healthy lives. In particular, some people continue to experience side effects on treatment - these may be life-threatening, may lead to a reduction in quality-of-life, and may limit the drugs that patients can receive in the future. If patients are unable to take their treatment for periods of time, then virus may grow that is resistant to some of the currently available drugs. An increasing number of HIV-positive people are living to older age, which may also lead to an increase in the side effects that are seen as well as an increase in general age-related illness. In addition, many HIV-positive children are also surviving into adulthood - as yet, we have little information on the outcomes of this group as they switch their care to adult HIV clinics. A proportion of people with HIV in the UK are also infected with hepatitis C virus (HCV) which has implications for the timing and choice of treatments that can be used. Whilst HCV has traditionally been hard to treat in those who also have HIV, some of the newly available HCV drugs offer greater promise of a cure for HCV. However, a large-scale assessment of the use of these drugs in people also infected with HIV remains to be undertaken. There are therefore many questions that must be addressed to ensure that the outcomes of those living with HIV are optimised. In particular, although it is often said that people with HIV can expect to live a 'near-normal' lifespan, whether this will ultimately be possible is far from clear. In order to plan the need for health care services and to understand the need for new drugs, it is essential that any changes in the characteristics of the UK epidemic are monitored.
Since 2001, the UK Collaborative HIV Cohort (CHIC) Study has followed people with HIV in the UK, to monitor their use of treatments against HIV and their outcomes. The UK HIV Drug Resistance Database (UK HDRD) collects information on the results of any tests that are performed to determine whether the virus that infects these individuals has become resistant to any of the currently used treatments. The latest dataset includes data on >45,000 patients attending 16 clinics and is one of the largest such collaborations worldwide. This application is for continued support of the combined UK CHIC Study and UK HDRD until 2019 for the following reasons:

1. To study the outcomes of people with HIV in the UK, including a description of the drugs that are used and any resistance that may develop;
2. To better understand of how HIV spreads between and within subgroups of the population;
3. To assess whether new and infrequently encountered strains of HIV are likely to respond less well to treatment;
4. To describe the use of new treatments for HCV in study participants, and to describe the success of these treatments, particularly in people who may get re-infected with HCV on multiple occasions;
5. To describe the outcomes of HIV-positive adolescents who switch their HIV care from paediatric to adult services and to model the likely problems that might result as the HIV population ages;
6. To explore the extent to which genetic factors might contribute to the outcomes of HIV and its treatment;
7. To investigate the potential effects of treatment, side effects and resistance on life expectancy in HIV-positive people.

A secondary aim is to continue to ensure that the UK plays a leading role in international HIV cohort research through the provision of high quality data to international studies.

Technical Summary

Whilst current combination antiretroviral (cART) regimens for HIV are extremely effective, there are many questions that remain to be addressed to ensure the optimal outcomes of HIV-positive people. In order to plan the need for health care services and to understand the need for new drugs, it is essential that any changes in the characteristics of the UK epidemic are monitored. These changes may arise from the changing demographics of the HIV-positive population, an increase in viral diversity, the introduction of new drugs, generic forms of existing drugs and changing treatment paradigms (e.g. a move towards earlier initiation of cART), as well as increased use of cART drugs as part of pre- or post-exposure prophylaxis against HIV. Surveillance of clinical and resistance outcomes is therefore required to inform national treatment policies. The primary aim of this application is to continue to expand and maintain the combined UK CHIC and UK HDRD database in order to answer a wide-ranging spectrum of questions relating to the clinical outcomes of those with HIV in the UK. The secondary aim is to continue to ensure that the UK plays a leading role in international HIV cohort research through the provision of high quality data and scientific input to major collaborative studies. The proposed research will be conducted in an environment at University College London that provides expertise in surveillance and audit studies, surveys of sexual behaviour, randomised trials, qualitative methods, mathematical modelling, behavioural and basic science research. UCL provides access to information technology and bioinformatics capability through the Farr Institute, with UCL Platform Technologies providing biobanks and informatic support. This setting therefore provides an ideal environment in which to conduct large-scale HIV cohort studies, with opportunities to translate study findings into interventions for those living with HIV and for wider public health benefit.

Planned Impact

The primary non-academic beneficiaries of our research are those living with HIV in the UK, their treating physicians, and the National Health Service (NHS). Our findings will, however, also have relevance for such individuals in countries other than the UK. Whilst our clinical findings have greatest relevance for those in other resource-rich settings, our research around resistance and transmission of HIV will be of relevance to resource-limited settings, particularly as antiretroviral therapy is rolled out more widely.

There are currently almost 100,000 people living with HIV in the UK. Despite the benefits of cART, it is estimated that the lifetime costs of HIV are £366,777. Thus, HIV continues to place a significant burden on the NHS. Even when treated, HIV is associated with a significant impact on quality of life (Duracinsky M, JAIDS, 2012). The Terence Higgins Trust/Age UK 50-Plus study (tht.org.uk) found that compared with their HIV-negative peers, HIV-positive people aged over 50 reported twice as many (non-HIV) long-term health conditions, had mobility problems and difficulties with everyday tasks, were less economically active, were less likely to have a financial cushion for old age and were more reliant on benefits. Any findings that result in further improvements in the way that people living with HIV are cared for, will likely result in substantial benefits to this population in the UK as well as their ability to remain in full-time employment, resulting in economic benefits for the country as a whole. The HIV patient community may additionally benefit through the increased capacity for work that may result.

The planning of health care services and antiretroviral drug prescribing must also be based on evidence. Changes to the UK HIV epidemic may arise from the changing demographics of the HIV-positive population (particularly the ageing population), an increase in viral diversity, the introduction of new drugs and changing treatment paradigms (e.g. earlier initiation of cART), as well as increased use of cART drugs as part of pre- (PrEP) or post-exposure prophylaxis against HIV. Whilst many of the recently licensed antiretroviral drugs are vulnerable to resistance, there is limited information on acquired and transmitted resistance to these drugs. Although the availability of generic drugs provides a significant potential for cost savings, concerns that the use of such drugs may be associated with lower rates of cART adherence (and therefore higher rates of treatment failure and resistance development) must be addressed. In particular, the use of more expensive novel agents in place of generics must be justified based on evidence. The impact of earlier initiation of cART and the roll-out of PrEP on the incidence of transmitted drug resistance and transmission of HIV is unknown. Finally, large-scale datasets are required to guide the diagnostic implementation and use of next generation sequencing methods in clinical practice. The information that is provided by this study will have a huge impact, therefore, on national treatment and care policies for those living with HIV with obvious financial benefits to the NHS. Our studies of associations with genotype may also identify new potential therapeutic targets, and the identification of genetic markers for stratification of patient management.
Our results also have implications for the wider population at risk of HIV infection. In particular, our research on HIV transmission dynamics and the extent of bridging between the MSM and heterosexual epidemics will provide important information for the development of interventions to prevent the transmission of HIV. Through the input to mathematical models, our results will be of use of public health professionals. These models have already been applied at an international level and have been used to inform global policy for ART programmes through work with WHO.

Publications

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AIDS-Defining Cancer Project Working Group For IeDEA And COHERE In EuroCoord (2017) Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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AIDS-Defining Cancer Project Working Group Of IeDEA, COHERE In EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. in AIDS (London, England)

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Antiretroviral Therapy Cohort Collaboration (ART-CC) (2016) Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis. in AIDS (London, England)

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Booth JW (2016) Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

 
Description Member of British HIV Association Guidelines Writing Group for the treatment of people living with HIV
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Individuals living with HIV receive treatment in line with the BHIVA guidelines - these are regularly updated and I have been a panel member since 2012. Over this time, survival of people living with HIV has improved.
 
Description NIHR Programme Development Grant (co-applicant).
Amount £100,000 (GBP)
Funding ID RP-DG-0517-10004 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2018 
End 03/2019
 
Description HIV-CAUSAL (Harvard University plus others) 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution Intellectual input into study design and analysis; provision of datasets; writing manuscripts
Impact Several publications in high impact journals, all are listed in appropriate section
Start Year 2009
 
Description The COBRA Study 
Organisation Imperial College School of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide the statistical support for the COBRA study, which also incorporates data from participants in the UK CHIC Study
Collaborator Contribution Neuroimaging, clinical medicine, biomarkers, immunology, virology, genetics, statistics, epidemiology
Impact One publication to date (listed in the form)
Start Year 2013
 
Description The COBRA Study 
Organisation VU University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution We provide the statistical support for the COBRA study, which also incorporates data from participants in the UK CHIC Study
Collaborator Contribution Neuroimaging, clinical medicine, biomarkers, immunology, virology, genetics, statistics, epidemiology
Impact One publication to date (listed in the form)
Start Year 2013
 
Description The POPPY Study 
Organisation Imperial College School of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Data from the UK CHIC study feeds into the POPPY Study (a cohort of HIV and ageing in the UK). The POPPY study has received funding from several funders, including the NIH, the British HIV Association and pharmaceutical companies, with around £200,000 coming to UCL over the next 3 years.
Collaborator Contribution Clinical management, neuroimaging, biomarker studies, HIV medicine, sleep medicine
Impact To date, two publications (listed on the form) have arisen from this collaboration. The collaboration is multi-disciplinary including HIV clinicians, neuroimagers, biomarker analysts, epidemiologists and statisticians.
Start Year 2013
 
Description UK HIV Drug Resistance Database 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution The studies have provided joint scientific leadership and have equally contributed to statistical analyses
Collaborator Contribution Through collaboration with this study we have successfully applied for a new five-year programme grant from the MRC (G0900274)
Impact Publications as listed in section 2 and further grant funding (described above)
 
Description Conference co-chair for AIDS 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact AIDS 2018 is the largest international HIV conference, attracting >20,000 participants from research, clinical, community, policy-maker and media settings. As Epidemiology Track co-Chair, my role is to develop the program for this five-day meeting, to ensure that the conference will meet its objectives for all attendees.
Year(s) Of Engagement Activity 2017,2018
 
Description Consultant for HIV Treatment Bulletin 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I act as a Consultant for HIV Treatment Bulletin, a not-for-profit community publication that aims to provide a review of the most important medical advances related to clinical management of HIV and its complications. This bulletin is widely recognized as an important source of information about the latest HIV research studies for patients, clinicians and policy makers.
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018
URL http://i-base.info/hiv-treatment-bulletin/
 
Description Founding member, SWIFT Network 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact The SWIFT network aims to promote research to improve the lives of women living with HIV. The network is organised and guided by a multidisciplinary group of community representative, clinicians and academics from across the UK and Ireland. Outputs from the network have included a list of community-identified priorities for research among women living with HIV, the identification of funding opportunities that may be appropriate, and the development of study teams that are tasked with pursuing funding applications.
Year(s) Of Engagement Activity 2015,2016,2017,2018
URL http://www.swift-women.co.uk/
 
Description Presentation on comorbidities at European AIDS Treatment Group. Ageing with HIV - New challenges and unmet needs of people living with HIV/AIDS aged 50+. Berlin, April 2016. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact The largely patient-based audience attended this three-day meeting at which they asked many questions about research relevant to their own experiences of ageing with HIV.
Year(s) Of Engagement Activity 2016
 
Description Provided advice on National AIDS Manual (NAM) factsheet on HIV and the ageing process, aimed at HIV community members 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact I provided advice on a National AIDS Manual (NAM) fact sheet on HIV and the ageing process, which is distributed free-of-charge to people living with HIV in the UK and elsewhere.
Year(s) Of Engagement Activity 2017
 
Description Talk on Disease registries and cohorts. UCL cohorts, biobanks & big data. London March 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Around 100 participants attended the meeting which was followed by a lively discussion about the role of cohort studies in supporting clinical decision making.
Year(s) Of Engagement Activity 2017
 
Description UK Community Advisory Board - development of community blog 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact We have recently started to work with our community team to develop a blog that will be linked to the UK-CAB website to provide updates on the HIV cohort studies. This is still in its infancy, as our community representative has no had experience in this role before - but we hope that this will go live later in 2017.
Year(s) Of Engagement Activity 2016
 
Description Workshop co-ordinator on Statistical methods for HIVNAT Bangkok International Symposium on HIV Medicine 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This workshop on Statistical methods was designed to increase capacity in statistical analysis in HIV cohort studies in Thailand and the Asia region. Around 50 participants, from a mixture of research, student, clinical and community backgrounds, participated in the meeting.
Year(s) Of Engagement Activity 2018