Poster No Slide Title Resistance

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					                            The UK HIV Drug Resistance Database: Development and use for national surveillance
                       Deenan Pillay1 and Hannah Green2 on behalf of the UK Collaborative Group on HIV Drug Resistance and the UK Register of HIV Seroconverters

                                                                                                       1. UCL, London, UK 2. MRC Clinical Trials Unit, London, UK
                    BACKGROUND                                                                        RESULTS                                       Treatment naïve vs Seroconverters
Determining the clinical correlates of HIV drug resistance, and                                                                                                                                                                                                    Treatment experienced:
                                                                         As of May 2003, 9798 test results, obtained since 1996, from             Of 152 seroconverters fulfilling the UK Register case definition,                                         % of patients with  1 primary mutation
estimation of resistance surveillance parameters, require large          6684 patients have been entered into the database. 60% of                26 (17%) had evidence of transmitted resistant HIV. Resistance
databases. A UK-wide non-proprietary collaboration of all                these patients have clinical data in the UK CHIC database. 2279          to any ART class was 15% between 1996-1998 before stabilising
virology laboratories and major clinical centres was established to      (23%) tests were performed whilst patients were naive to                 at 18% from 1999 onwards. The prevalence of resistance over
pool resistance data and interpretation patterns, together with          treatment and 5815 (59%) on treatment experienced patients.              time was similar to resistance in treatment naïve patients.                                    80
pre- and post- test virological, clinical and therapeutic information.   The treatment status of the remaining 1704 (17%) tests is                                                                                                               70
Resistance data is generated by “in house”, VGI (Bayer), and ABI         unknown. Resistance test failures and tests with missing results
(Abbott) sequencing methodologies as well as by VIRCO.                   are excluded from further analyses.
                                                                                                                                                         % of patients with  1 primary mutation (any class)                                     50
We describe the first outputs from the UK database; the                            Number of tests by year and treatment status                                                                                                                  40
prevalence of resistance in treatment naïve patients, patients with
                                                                                                                                                   20                                                                                            30
acute/recent infections (seroconverters) and treatment
experienced patients.                                                      2500                                                                                                                                                                  20
                                                                                                                                                   12                                                                                              0
                        METHODS                                            1500
                                                                                                                                                   10                                                                                                   1996-7       1998       1999        2000        2001      2002-3
                                                                                                                                                                                                                                                                    NRTI         PI        NNRTI          Any Class
Clinical data                                                              1000
Without related clinical information, resistance data are of limited
value. Clinical data were obtained from electronic databases                500                                                                      2

wherever possible including the UK Collaborative HIV Cohort                                                                                          0
                                                                              0                                                                              1996-1998            1999-2000             2001-2003
study (UK CHIC). If no accurate clinical database was available,
clinics were asked to complete a standard form.
                                                                                    1996-7    1998     1999      2000     2001       2002-3
                                                                                                                                                                             Naive    Seroconverters
                                                                                  Treatment naive     Treatment experienced      Status unknown

Treatment status                                                                                                                                                                                                                              • A large HIV-1 drug resistance clinical database containing nearly
The ART treatment status of patients (naïve to treatment or                                                                                                                                                                                   10,000 results has been successfully established in the UK. The
experienced) at the time of each resistance test was determined
                                                                                                Treatment naïve                                                   Treatment experienced                                                       clinical data related to these results have been and will continue to
either by using clinical data or the reason for the test given on the                                                                                                                                                                         be audited for accuracy.
resistance test request form.                                            1966 patients had a resistance test whilst naïve to ART treatment;       For treated patients, resistance to any ART class remained stable
                                                                         270 (14%) with evidence of resistant HIV. For the time periods           over time (71%, 78 %, 78% for time periods 1996-1998, 1999-                                 • Approximately 15% of drug naïve patients who have had a
Various checks were made on a sample of patients thought to be           1996-1998, 1999-2000 and 2001-2003, resistance to any ART                2000 and 2001-2003 respectively). NNRTI resistance                                          resistance test are infected with virus with at least one key
naïve to confirm treatment history prior to the resistance test:         class was 9%, 15% and 16% respectively. NRTI resistance                  significantly increased over time with the rate of increase                                 resistance associated mutation.
• Resistance test request forms were manually checked for                followed a similar trend. After an initial rise in PI and NNRTI          declining in recent years. PI resistance peaked in 1999 before
additional ART information                                               resistance, there is no clear trend after 1999.                          stabilising at 27% in the 2001-2003 period. There was no                                    • Little difference is observed in prevalence of resistance when
• Patient notes were manually checked to assess the accuracy of                                                                                   evidence of a trend in NRTI resistance.                                                     comparing nearly 2000 drug naïve individuals with a smaller group
treatment history contained in the UK CHIC database.                     Prevalence of resistance was not associated with risk group,                                                                                                         of seroconverters. This suggests that surveillance of chronic drug
Out of a sample of 72 patients checked, 7 were found to be               ethnic origin or the closest CD4 measurement to the test date.                                                                                                       naïve patients may be useful for monitoring transmitted drug
                                                                                                                                                                          1996-1998           1999-2000         2001-2003                     resistance. However, because they are chronically infected (in
treatment experienced at the time of the resistance test.
                                                                                                                                                                                                                                              contrast with seroconverters), the prevalence observed in a given
Resistance                                                                                        Treatment naive:                                                                                                                            calendar period does not necessarily reflect the level of
                                                                                                                                                          Any class           71%                78%                78%
Resistance was defined as at least one key (primary) mutation                          % of patients with  1 primary mutation                                                                                                                transmitted resistance at that point in time.
according to IAS-USA (2003). The analysis was based on the                  25                                                                            NRTI                67%                71%                70%
first test for each patient whilst naïve to ART treatment and the                                                                                         PI                  26%                32%                27%                       • Future uses of the database will focus on virological predictors of
first test per year when treatment experienced.                                                                                                           NNRTI               20%                39%                49%                       treatment response, in addition to continual surveillance of drug
                                                                            20                                                                                                                                                                resistance in drug naïve and experienced patients.
Tests reported to have been undertaken in „seroconverters‟ are              15
followed up through the UK Register of Seroconverters to
establish whether they fulfil a common case definition; that the            10
                                                                                                                                                  UK Collaborative Group on HIV Drug Resistance Steering Committee:
resistance test was performed within 18 months of a documented                                                                                    Judy Breuer, Sheila Burns, Sheila Cameron, Ian Chrystie, Duncan Churchill, John Clarke, David Dunn, Philippa Easterbrook, Barry Evans, David Goldberg, Mark Gompels, Teresa
negative HIV antibody test or laboratory confirmed acute infection           5                                                                    Hill, Paul Kellam, Andrew Leigh-Brown, Clive Loveday, Ryanne Matthias, Anna Maria Murdin-Geretti, Andrew Phillips, Deenan Pillay, Kholoud Porter, Anton Pozniak, Caroline
in an ART-naïve individual. Data from the UK register was used                                                                                    Sabin, Peter Tilston, Ian Williams
                                                                                                                                                  UK Register Steering Committee:
to measure the prevalence of resistance amongst patients with                                                                                     Abdel Babiker, Valerie Beral (Chair), Ray Brettle, Chris Carne, Janet Darbyshire, Philippa Easterbrook, Noël Gill, Richard Gilson, David Goldberg, David Hawkins, Don Jeffries,
acute/recent infections.                                                                                                                          Anne Johnson, Margaret Johnson, George Kinghorn, Linda Lazarus, Ken McLean, Philip Mortimer, Andrew Phillips, Deenan Pillay, Sarah Rowland-Jones, Jonathan Weber, Ed
                                                                                    1996-7     1998     1999      2000        2001    2002-3
                                                                                                                                                  Wilkins; Coordinator: Kholoud Porter
                                                                                              NRTI      PI      NNRTI         Any Class           Contact:

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