HIV Epidemiology

Lead Research Organisation: MRC Clinical Trials Unit

Abstract

This is mainly a programme of studies following up adults and children with HIV and fits in well with the clinical trials programme. This is because these studies can highlight areas where more investigative studies like clinical trials need to be done. They are also important in helping statisticians to design these trials and allow us to follow people up over the longer term to see how they do beyond the time that they re in the clinical trials.||The observational studies in adults are the UK Register of HIV Seroconverters, which led to a bigger collaboration called CASCADE funded by the European Commission, and which the UK Register is now part of. CASCADE was first funded in 1997 and brings together experts conducting 23 studies in 15 European countries, Australia and Canada. The studies have one thing in common in that they are of HIV infected people for whom we have a reasonably accurate date of when they became infected, or seroconverted. Information from these seroconverters allow us to follow-up people who ve recently become infected throughout the whole period since they came in contact with the virus.||A study in children called CHIPS (Collaborative HIV Paediatric Study) was established in April 2000, and follows-up HIV infected children in the UK and Ireland. CHIPS is a collaboration between centres caring for HIV-infected children, many of whom are enrolled in PENTA trials (the Paediatric European Network for the Treatment of AIDS), the National Study of HIV in Pregnancy and Childhood (NSHPC) at the Institute of Child Health, and the MRC CTU. The main objectives of CHIPS are to describe clinical, laboratory and treatment data for these children, as well as their use of paediatric HIV services. CHIPS aims to enhance the exchange of information and expertise between centres in order to promote standardised high quality paediatrician-led care of all HIV-infected children in the UK and Ireland.||The UK HIV Drug Resistance Database is a central repository for resistance tests performed as part of routine clinical care throughout the UK. Established in 2001, by the end of 2007 over 51,000 test results have been received and stored. A key feature of the Database is extensive patient-level linkage with several clinical cohorts and surveillance databases in the UK. This has allowed analyses which have given important insights into the epidemiology and clinical aspects of HIV drug resistance.||Evidence for Action (EfA) is a five-year international research programme funded from the UK Department for International Development. EfA focuses on HIV treatment and care systems and the goal of the research programme is to contribute to knowledge on how to design, manage and deliver comprehensive HIV treatment and care programmes in resource-poor settings. The programme will provide evidence-informed, practical recommendations to policy makers, programme managers and funding agencies on how to maximise the benefits and equity of HIV treatment & care systems in developing countries.

Technical Summary

The HIV epidemiology programme largely comprises cohort studies and cohort collaborations, in adults and children, and complements the clinical trials programme. These observational studies raise questions which may then be answered by trials and are a necessary resource for trial design and sample size calculations. They also contribute to the assessment of long-term outcomes.||In adults, the UK Register of HIV Seroconverters has formed the basis for an HIV cohort collaboration (CASCADE), first established in 1997 and maintained through several successful EU funding bids, between the investigators of 23 cohorts of persons with well-estimated dates of HIV seroconversion (~20,000 seroconverters). It is currently a network of epidemiologists, statisticians, virologists and clinicians from lead HIV institutions in 15 European countries, Australia and Canada. Seroconverters are enrolled into the individual cohorts locally and nationally and are typically followed up life-long. CASCADEs main aim is to monitor newly infected individuals and those already enrolled in studies, covering the entire duration of HIV infection. The main premise is that through pooling data issues can be addressed, which cannot be reliably addressed from single studies alone.||In children, The Collaborative HIV Paediatric Study (CHIPS) was established in April 2000, and is a multi-centre cohort study of HIV infected children in the UK and Ireland. CHIPS is a collaboration between centres caring for HIV-infected children, many of whom are enrolled in PENTA trials (the Paediatric European Network for the Treatment of AIDS), the National Study of HIV in Pregnancy and Childhood (NSHPC) at the Institute of Child Health, and the MRC CTU. The main objectives of CHIPS are to describe clinical, laboratory and treatment data for these children, as well as their use of paediatric HIV services. CHIPS aims to enhance the exchange of information and expertise between centres in order to promote standardised high quality paediatrician-led care of all HIV-infected children in the UK and Ireland.||The UK HIV Drug Resistance Database is a central repository for resistance tests performed as part of routine clinical care throughout the UK. Established in 2001, by the end of 2008 over 51,000 test results have been received and stored. Most of these (around 90%) are in the form of viral gene sequences. A key feature of the Database is extensive patient-level linkage with several clinical cohorts and surveillance databases in the UK. This has allowed analyses which have given important insights into the epidemiology and clinical aspects of HIV drug resistance.||Evidence for Action (EfA) is a five-year international research programme with core funding from the UK Department for International Development. EfA focuses on HIV treatment and care systems and the goal of the research programme is to contribute to knowledge on how to design, manage and deliver comprehensive HIV treatment and care programmes in resource poor settings. The programme will provide evidence-informed, practical recommendations to policy makers, programme managers and funding agencies on how to maximise the benefits and equity of HIV treatment & care systems in developing countries.

Publications

10 25 50

 
Description Conference on poverty-related diseases
Geographic Reach Europe 
Policy Influence Type Participation in advisory committee
Impact Dr Porter was invited to present at the conference
 
Description EMEA Biotechnology working party
Geographic Reach Europe 
Policy Influence Type Participation in a national consultation
Impact Dr Porter is the UK Representative on the Biotechnology Working Party Epidemiology Group for the European Agency for the Evaluation of Medicinal Products (EMEA); recommendations for the use of plasmapheresis from companies in countries recently joining the EU
 
Description HIV/AIDS Think Tank forum
Geographic Reach Europe 
Policy Influence Type Participation in advisory committee
Impact Dr Porter was invited to give a presentation at the forum
 
Description NICE HBV Appraisal Committee
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Dr Dunn was part of the review board of Adefovir dipivoxil and pegylated interferon alpha-2a for the treatment of chronic hepatitis B; Recommendation of use in hepatitis B infection
 
Description NICE HCV Appraisal Committee
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Expanded indications for treatment of HCV
 
Description WHO Incidence Working Group
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Dr Porter was invited to present to the working group
 
Description WHO paediatric HIV guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Has affected international/national guidelines
 
Description CASCADE (1.7m euros across 25 participants)
Amount £55,760 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2006 
End 06/2010
 
Description CHAIN Collaborative HIV and Anti-HIV Drug Resistance Network (10m euros across 24 participants)
Amount £341,601 (GBP)
Funding ID 223131 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 04/2009 
End 03/2014
 
Description DFID, Project Grant
Amount £3,749,247 (GBP)
Organisation Government of the UK 
Department Department for International Development (DfID)
Sector Public
Country United Kingdom
Start 01/2007 
End 06/2011
 
Description DoH project grant/UK Department of Health
Amount £250,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2007 
End 04/2010
 
Description EC FP7
Amount £1,571,500 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 01/2011 
End 12/2015
 
Description EUROCOORD (12m euros across 23 participants)
Amount £427,826 (GBP)
Funding ID 260694 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2011 
End 12/2015
 
Description European Union DG Sanco
Amount £300,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2007 
End 02/2010
 
Description MRC Programme Grant
Amount £2,226,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2009 
End 08/2014
 
Description MRC Project Grant
Amount £1,023,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2007 
End 01/2010
 
Description MRC Project Grant
Amount £858,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2006 
End 06/2009
 
Description UK HIV Drug Resistance Database
Amount £2,125,277 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 10/2019
 
Title Competing risks practical guide 
Description A practical guide on modelling competing risks data has been prepared and made freely available on the CASCADE website (www.cascade-collaboration.org) for download. The guide briefly introduces the different theoretical approaches to model competing risks data, and focuses on cause-specific and cumulative incidence models, describing their implementation in widely used statistical software (i.e., Stata and/or R). Guidelines on downloading R (free software) and its relevant modules are provided in the appendix. Additionally, the different methods to treat time to a competing event are compared and discussed using examples from the CASCADE database 
Type Of Material Data analysis technique 
Year Produced 2007 
Provided To Others? Yes  
Impact The guide is being used by statisticians and epudemiologists within the CASCADE Collaboration for analysing longitudinal data in the presence of competing risks (e.g. AIDS events and death) 
URL http://www.cascade-collaboration.org
 
Title Modelling the association between patient characteristics and the change over 
Description Published in Statistics In Medicine (PubMed ID 19768690) 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact none 
 
Description CASCADE 
Organisation Hopital Bicetre
Country France 
Sector Hospitals 
PI Contribution Kholoud Porter is Project Leader and will also lead a new FP7-funded Network of Excellence, which will incorporate CASCADE as well as all other HIV European cohorts, from 1st January 2011
Collaborator Contribution Publications and securing FP7 funding
Impact CASCADE is a network of 25 cohorts from Europe, Canada, Australia and Africa with >20,000 HIV-infected individuals, drawn from >300 clinics, with early diagnosis of HIV infection and known time period of HIV seroconversion. The network of experts in the diagnosis, management, and analyses of data from individuals with primary HIV infection, is in a unique position to study the full course of HIV infection using data from these individuals. Furthermore, seroconverters are, by definition, optimally identified and have the best chances of access to treatment. They represent, therefore, the ideal of what may be achieved through early testing and presentation, and set a gold standard against which to compare the outcome of all infected individuals. CASCADE aims focus on identification of early HIV infection and research questions requiring knowledge of the time of seroconversion. Specifically, the network aims to identify and characterize newly-acquired infection, its contribution to the propagation of the epidemic, and to monitor short and long-term outcome and their determinants, especially in terms of the host, HIV and the relationship between the two.
 
Description CHAIN 
Organisation University College London
Department MRC Centre for Medical Molecular Virology
Country United Kingdom 
Sector Public 
PI Contribution MRC is a beneficairy and is a major contribution to 3 work packages
Collaborator Contribution Networking
Impact several publications
Start Year 2009
 
Description DHICE 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution MRC is beneficiary
Collaborator Contribution Collaboration is the basis for the research
Impact Enhancing use of patient electronic data for HIV clinical research
Start Year 2008
 
Description EuroCoord NoE 
Organisation European Commission
Department Seventh Framework Programme (FP7)
Country European Union (EU) 
Sector Public 
PI Contribution MRC CTU is Project Lead
Collaborator Contribution Sharing of data, resources and know-how
Impact The following guidelines: US Department of Health and Human Services- Treatment of adults and adolescents, and perinatal with HIV, and prevention and treatment of opportunistic infections WHO- Consolidated HIV treatment and prevention guidelines International AIDS Society- Adult HIV treatment guidelines, and HIV drug resistance testing British HIV Association- HIV treatment guidelines, management of Hepatitis viruses, HIV routine investigation and monitoring, and treatment of opportunistics infections This is a multi-disciplinary collaboration: clinical, epidemiology, statistics, virology, immunology, genetics, public health, bio-informatics, IT
Start Year 2011
 
Description Improving monitoring of the continuum of HIV 
Organisation Amsterdam Medical Center
Department Clinical Immunology and Rheumatology KIR (AMC-R)
Country Netherlands 
Sector Hospitals 
PI Contribution Following on from an earlier funded collaboration, I led a consortium funded by ECDC comprising colleagues from INSERM (DR Paris 6), National and Kapodistrian University of Athens, Academic Medical Center (Amsterdam) and the National Institute of Public Health- National Institute of Hygiene (Warsaw). The aim is to improve the monitoring of the HIV continuum of care by synthesising and further developing definitions, improving data sources, and identifying ways of overcoming some of the challenges faced in constructing HIV continuums. Specifically: • Describing the rational for measuring and monitoring a four-point continuum of HIV care. • Providing advice regarding options for European countries in measuring the continuum of HIV care, given their available data sources. • Describing how countries in the WHO European Region are meeting the UNAIDS 90-90-90 target by summarising continuum of HIV care data, collected through activities monitoring the Dublin Declaration.
Collaborator Contribution Providing expert technical support to countries to assist them in developing their capacity to construct national continuums of HIV care, through training (e.g. on modelling) or by recommending suitable methods and possible enhancements to data collection systems, as necessary and feasible Construction of HIV care continuums by key populations using clinical cohort and HIV surveillance data Methodological development of HIV continuum of care concepts, broadly contributing to the development of definitions for the continuum of care, but specifically exploring the feasibility and utility of using longitudinal measures related to timeliness of each element, such as the time from HIV infection to diagnosis
Impact The outputs have all been in the form of publications (included) in the relevant section The collaboration is not multi-disciplinary
Start Year 2016
 
Description Improving monitoring of the continuum of HIV 
Organisation European Centre for Disease Prevention and Control (ECDC)
Country European Union (EU) 
Sector Public 
PI Contribution Following on from an earlier funded collaboration, I led a consortium funded by ECDC comprising colleagues from INSERM (DR Paris 6), National and Kapodistrian University of Athens, Academic Medical Center (Amsterdam) and the National Institute of Public Health- National Institute of Hygiene (Warsaw). The aim is to improve the monitoring of the HIV continuum of care by synthesising and further developing definitions, improving data sources, and identifying ways of overcoming some of the challenges faced in constructing HIV continuums. Specifically: • Describing the rational for measuring and monitoring a four-point continuum of HIV care. • Providing advice regarding options for European countries in measuring the continuum of HIV care, given their available data sources. • Describing how countries in the WHO European Region are meeting the UNAIDS 90-90-90 target by summarising continuum of HIV care data, collected through activities monitoring the Dublin Declaration.
Collaborator Contribution Providing expert technical support to countries to assist them in developing their capacity to construct national continuums of HIV care, through training (e.g. on modelling) or by recommending suitable methods and possible enhancements to data collection systems, as necessary and feasible Construction of HIV care continuums by key populations using clinical cohort and HIV surveillance data Methodological development of HIV continuum of care concepts, broadly contributing to the development of definitions for the continuum of care, but specifically exploring the feasibility and utility of using longitudinal measures related to timeliness of each element, such as the time from HIV infection to diagnosis
Impact The outputs have all been in the form of publications (included) in the relevant section The collaboration is not multi-disciplinary
Start Year 2016
 
Description Improving monitoring of the continuum of HIV 
Organisation National Institute of Health and Medical Research (INSERM)
Department Inserm/UPS UMR 1048 Institute of Metabolic and Cardiovascular Diseases (I2MC)
Country France 
Sector Public 
PI Contribution Following on from an earlier funded collaboration, I led a consortium funded by ECDC comprising colleagues from INSERM (DR Paris 6), National and Kapodistrian University of Athens, Academic Medical Center (Amsterdam) and the National Institute of Public Health- National Institute of Hygiene (Warsaw). The aim is to improve the monitoring of the HIV continuum of care by synthesising and further developing definitions, improving data sources, and identifying ways of overcoming some of the challenges faced in constructing HIV continuums. Specifically: • Describing the rational for measuring and monitoring a four-point continuum of HIV care. • Providing advice regarding options for European countries in measuring the continuum of HIV care, given their available data sources. • Describing how countries in the WHO European Region are meeting the UNAIDS 90-90-90 target by summarising continuum of HIV care data, collected through activities monitoring the Dublin Declaration.
Collaborator Contribution Providing expert technical support to countries to assist them in developing their capacity to construct national continuums of HIV care, through training (e.g. on modelling) or by recommending suitable methods and possible enhancements to data collection systems, as necessary and feasible Construction of HIV care continuums by key populations using clinical cohort and HIV surveillance data Methodological development of HIV continuum of care concepts, broadly contributing to the development of definitions for the continuum of care, but specifically exploring the feasibility and utility of using longitudinal measures related to timeliness of each element, such as the time from HIV infection to diagnosis
Impact The outputs have all been in the form of publications (included) in the relevant section The collaboration is not multi-disciplinary
Start Year 2016
 
Description Improving monitoring of the continuum of HIV 
Organisation National and Kapodistrian University of Athens
Department University of Athens Medical School
PI Contribution Following on from an earlier funded collaboration, I led a consortium funded by ECDC comprising colleagues from INSERM (DR Paris 6), National and Kapodistrian University of Athens, Academic Medical Center (Amsterdam) and the National Institute of Public Health- National Institute of Hygiene (Warsaw). The aim is to improve the monitoring of the HIV continuum of care by synthesising and further developing definitions, improving data sources, and identifying ways of overcoming some of the challenges faced in constructing HIV continuums. Specifically: • Describing the rational for measuring and monitoring a four-point continuum of HIV care. • Providing advice regarding options for European countries in measuring the continuum of HIV care, given their available data sources. • Describing how countries in the WHO European Region are meeting the UNAIDS 90-90-90 target by summarising continuum of HIV care data, collected through activities monitoring the Dublin Declaration.
Collaborator Contribution Providing expert technical support to countries to assist them in developing their capacity to construct national continuums of HIV care, through training (e.g. on modelling) or by recommending suitable methods and possible enhancements to data collection systems, as necessary and feasible Construction of HIV care continuums by key populations using clinical cohort and HIV surveillance data Methodological development of HIV continuum of care concepts, broadly contributing to the development of definitions for the continuum of care, but specifically exploring the feasibility and utility of using longitudinal measures related to timeliness of each element, such as the time from HIV infection to diagnosis
Impact The outputs have all been in the form of publications (included) in the relevant section The collaboration is not multi-disciplinary
Start Year 2016
 
Description UK HIV Drug Resistance Database 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Lead the collaboration
Collaborator Contribution The collaboration is the basis for the researchadvancing knowledge in HIV drug rseistance
Impact Multiple papers on HIV drug resistance (surveillance of transmitted drug resistance, molecular epidemiology, clinical aspects)
 
Description Cotrimoxazole Prophylaxis Policy Group. Identifying and minimising the gap between knowledge, policy and practice in relation to the use of Cotrimoxazole prophylaxis in adult and paediatric HIV care. XVII International AIDS Conference Mexico City 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Policymakers/politicians
Results and Impact The paper highlighted the gap between research findings and implementation into policy and practice. The example used is the use of Cotrimoxazole as prophylaxis for HIV infected adults and children in developing countries- although clear evidence known for some time, and low cost, governments and policy makers have been slow to implement.

None at present
Year(s) Of Engagement Activity 2008
 
Description Evaluating outcome indicators used to assess the performance of HIV programmes of treatment and care in resource-limited countries. XVII International AIDS Conference Mexico City 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Policymakers/politicians
Results and Impact The paper argued for the need of an evaluation of indicators used to monitor the success of HIV treatment and care programmes in resource-limited countries as a direct assessment of survival and HIV drug resistance within these programmes is problematic and the indicators used as proxy measures to monitor these outcomes have not been evaluated programmatically

A meeting with the Global Fund to evaluate funding project is set for February 2010
Year(s) Of Engagement Activity 2008
 
Description UK HIV Drug Resistance Database 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact many questions

x
Year(s) Of Engagement Activity 2010