1. The UK Collaborative HIV Cohort (UK CHIC) Study

2. Background
Information on HIV infection in the UK comes from a variety of sources; these are often limited in scope
Many clinical centres routinely collect information about HIV-positive patients when they attend:
This provides an ideal opportunity to study HIV-positive individuals in their clinical setting.
Existing infrastructure can be used for data collection.
Patients from a wide variety of clinics are included so that the cohort becomes more representative of HIV-positive people in the UK.

3. UK CHIC: Objectives
UK CHIC initiated in 2001 to collate routinely collected data from HIV-positive patients attending some of the largest clinical centres in the UK since 1st January 1996
Specific aims are:
to describe the characteristics of patients with HIV under care
to provide information on exposure to combination antiretroviral therapy (cART) and changes to the immunological, virological and clinical status of patients over time
to monitor the frequency of AIDS and survival over time.

4. UK CHIC: Participating clinics
Clinical centres
Brighton and Sussex University Hospitals NHS Trust
York Teaching Hospital NHS Foundation Trust
Chelsea & Westminster NHS Trust
Coventry, University Hospitals Coventry and Warwickshire NHS Trust
Mortimer Market Centre,
Central and NW London NHS Foundation Trust
Wolverhampton, The Royal Wolverhampton NHS Trust
Kings College Hospital NHS Trust
Chertsey, Ashford and St Peter’s Hospitals NHS Foundation Trust
Royal Free NHS Trust
St Mary’s, Imperial College Healthcare NHS Trust
Barts and the London NHS Trust
Homerton University Hospital NHS Trust
Edinburgh, The Lothian University Hospitals NHS Trust
North Middlesex University Hospital NHS Trust
Collaborators
North Bristol NHS Trust
Research Dept. of Infection and Population Health, UCL
Leicester, University Hospitals of Leicester NHS Trust
Medical Research Council Clinical Trials Unit at UCL
Middlesbrough, South Tees Hospitals NHS Foundation Trust
Public Health England (formerly HPA-CfI)
Woolwich, South London Healthcare NHS Trust
St George’s Healthcare NHS Trust
New centres joining the collaboration:
These centres will be in chic2013 dataset:
Wolverhampton - The Royal Wolverhampton NHS Trust
Coventry - University Hospitals Coventry and Warwickshire NHS Trust
Chertsey – Ashford and St Peter’s Hospitals NHS Foundation Trust
Future:
Newham University Hospital, Barts Health NHS Trust, London
St. Thomas’ Hospital, London - Guy’s and St Thomas’ NHS Foundation Trust

5. Inclusion criteria Patients:
aged > 16 years and seen at any of the centres since 1/1/1996
Clinics:
electronic data are already available
able to provide data on an annual basis

6. Funding Study funded by the MRC since 2001 Funding provides:
some database programming support
project co-ordination
statistical support
limited funding for clinics for provision of data
The database is physically located at MRC CTU – centrally located and ‘independent’ of all clinical centres
The project co-ordinator and principal investigator are based at UCL (Royal Free campus)

7. Study management Steering committee meets every 3-6 months
with representatives from:
- each clinical centre
- the coordinating centre
- the UK Resistance Database
- the patient community
Specific sub-groups:
- data management
- viral hepatitis co-infection
- pregnancy
- HIV and ageing
- renal outcomes

8. Data protection policy
Policy drafted by a sub-group with input from experts in health informatics.
Data are submitted by secure web-based transfer (FTP), plus encryption.
Database access is restricted and monitored.
Datasets released for research analyses are approved by the steering committee, are anonymised, and only include necessary data.
Personnel with access to the data are made aware of data confidentiality requirements.

9. Processes Datasets and formats agreed upon by all centres
Data sent to coordinator by centres
Data checked for consistency
Data entered into main database; error and logical checks performed
Datasets and formats agreed upon by all centres
Data from all centres merged and possible duplicates identified
Final dataset distributed for analysis
Errors checked
and corrected on source and submitted dataset
Results fed back to clinics and data managers
Subset of records audited

10. Datasets Demographics
(patient, centre, ethnicity, risk group, first and last attendance)
Clinical events
- AIDS
- serious non-AIDS
- death
Antiretroviral
therapy
Hepatitis
- A/B/C tests
- clinical data
Laboratory-defined toxicities
Adherence
Prophylaxis (PCP)
(No longer collected)
CD viral loads
HLA-B*5701
Attendance ?
future data items
Hepatitis, Adherence and Toxicity data collected from 2004 onwards
HLAB57 and Attendance data collected form 2009 onwards
Hepatitis additional data collected in , from 2006 onwards,
includes hep treatment, liver scans, clinical data

11. Data quality checks
missing data items (demographics, drug names, CD4/CD8 counts, HIV RNA)
duplicate patients within same centre
duplicate laboratory measurements or AIDS events
undetectable viral load at start of treatment
CD4 or CD8 counts of zero
inconsistent data and dates (e.g. HIV+ve date before HIV-ve date, any odd or future dates)
overlapping drug start/stop dates
All queries are investigated and both CHIC and clinic databases are updated with corrected information

12. De-duplication process
Individuals may have attended more than one clinical centre.
Potential matches identified by matching date of birth and soundex; other demographic variables are used to determine whether potential matches are definite or indeterminate, e.g.
- HIV+ve dates in same calendar year
- dates of death within 1 month
- transferred to/from same centre
- first/last seen dates are consistent
- same country of birth (non-UK only)
Once duplicate patients have been identified, data from individual records are combined.

13. Improving death data
Many patients do not ‘reappear’ at their clinics for long periods of time; some of these may have left the country and/or may have died.
UK CHIC records are matched to records held at the PHE (which include death data from the Office of National Statistics)
Matches are sent to centres to check that no evidence exists that the patient is still alive; when confirmed, the database is updated.
From 2010, ONS data not available at the MRC CTU. Individual studies now have to apply for access to ONS data. Through the DHICE project, death data could be supplemented from ONS data obtained by the HPA (HPA has access to ONS data).
HPA will have ONS data for deaths up to 65 years of age, extra data are beneficial as life expectancy with HIV is increasing.
Extra death info also obtained from CoDe forms.
Will try and incorporate into CHIC more info on causes of death – recorded in ONS data from June 2001 onwards, and from CoDe forms (2006 onwards).

14. Audit of data 1% of records from each centre are audited.
Each record ‘recreated’ using data obtained from clinical notes and compared with information stored on database (not CD4 or viral load).
Exact match required for demographic data, and date to within 1 month for dates of starting ART and AIDS events.
Demographic data generally reasonable (a few problems with ethnicity and country of birth); some discrepancies in AIDS events or dates.
Some AIDS events and ARV drugs found in notes but not database and vice versa.

15. Link to UK HIV Drug Resistance Database
UK CHIC is linked with UK Collaborative Group on HIV Drug Resistance, set up in 2001 to collect information on routinely performed resistance tests in the UK.
Resistance test data (sequences) are collected.
There is substantial overlap of patients in the two databases so clinical information is shared.
Results of over 106,000 resistance tests relating to 66,100 patients are stored on the database – 24,700 patients have linked clinical data in the UK CHIC study (data to end of 2012).
Resistance tests for CHIC patients – Number of patients + Resist test that are in CHIC = 24,700/50,785 = (48.6%)
Anna Tostevin currently doing data linkage 2014

16. Key findings

17. Characteristics of cohortn %
Total number of patients
50785
100.0
Sex:
Male
Female
36645
14140
72.2
27.8
Risk group:
MSM
IDU
24799
1710
48.8
3.4
Heterosexual
Other/not known
18950
5326
37.3
10.5
Ethnicity:
White
26517
52.2
Black African
14107
Black Other
2686
5.3
Other/Not known
7475
14.7
Deaths
4639
9.1
CHIC 2013 dataset

18. Study outputs

19. Collaborations TDM Registry University of Liverpool
Collaborative HIV Paediatric Study (CHIPS)
European COHERE collaboration
UK HIV Drug Resistance database
National Study of HIV in Pregnancy and Childhood (NSHPC)
TDM Therapeutic Drug Monitoring
NSHPC (Pat Tookey) and London HIV perinatal research group
Methodology groups Bristol- Jonathan Sterne, Margaret May
Statistical research/ methodology groups
Public Health England
(surveillance)

20. Acknowledgements Steering Committee:
Jonathan Ainsworth, Sris Allan, Jane Anderson, Abdel Babiker, David Chadwick, Valerie Delpech, David Dunn, Martin Fisher, Brian Gazzard, Richard Gilson, Mark Gompels, Phillip Hay, Teresa Hill, Margaret Johnson, Sophie Jose, Stephen Kegg, Clifford Leen, Fabiola Martin, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Caroline Sabin (PI), Memory Sachikonye, Achim Schwenk, Anjum Tariq, John Walsh.
Central Co-ordination: Teresa Hill, Sophie Jose, Andrew Phillips, Caroline Sabin, Alicia Thornton, Susie Huntington (UCL); David Dunn, Adam Glabay (Medical Research Council Clinical Trials Unit [MRC CTU at UCL])
Participating sites:
Brighton and Sussex University Hospitals NHS Trust (M Fisher, N Perry, S Tilbury, E Youssef, D Churchill); Chelsea and Westminster Hospital NHS Foundation Trust, London (B Gazzard, M Nelson, R Everett, D Asboe, S Mandalia); King’s College Hospital NHS Foundation Trust, London (F Post, H Korat, C Taylor, Z Gleisner, F Ibrahim, L Campbell); Mortimer Market Centre, University College London (R Gilson, N Brima, I Williams); Royal Free NHS Foundation Trust/University College London (M Johnson, M Youle, F Lampe, C Smith, R Tsintas, C Chaloner, S Hutchinson, C Sabin, A Phillips, T Hill, S Jose, A Thornton, S Huntington); Imperial College Healthcare NHS Trust, London (J Walsh, N Mackie, A Winston, J Weber, F Ramzan, M Carder); Barts and The London NHS Trust, London (C Orkin, J Lynch, J Hand, C de Souza); Homerton University Hospital NHS Trust, London (J Anderson, S Munshi); North Middlesex University Hospital NHS Trust, London (J Ainsworth, A Schwenk, S Miller, C Wood); The Lothian University Hospitals NHS Trust, Edinburgh (C Leen, A Wilson, S Morris); North Bristol NHS Trust (M Gompels, S Allan); Leicester, University Hospitals of Leicester NHS Trust (A Palfreeman, K Memon, A Lewszuk); Middlesbrough, South Tees Hospitals NHS Foundation Trust (D Chadwick, E Cope, J Gibson); Woolwich, Lewisham and Greenwich NHS Trust (S Kegg, P Main, Dr Mitchell, Dr Hunter), St George’s Healthcare NHS Trust (P Hay, M Dhillon); York Teaching Hospital NHS Foundation Trust (F Martin, S Russell-Sharpe); Coventry, University Hospitals Coventry and Warwickshire NHS Trust (S Allan, A Harte, S Clay); Wolverhampton, The Royal Wolverhampton Hospitals NHS Trust (A Tariq, H Spencer, R Jones); Chertsey, Ashford and St Peter’s Hospitals NHS Foundation Trust (J Pritchard, S Cumming, C Atkinson); Public Health England, London (V Delpech); UK Community Advisory Board (M Sachikonye).
List is appropriate for the chic2013 data submission and preparation, so may not include the latest staff at centres.
Funding:
UK CHIC is funded by the UK Medical Research Council