HLA Testing: A Single Centre Experience

1
HLA Testing A Single Centre Experience

• Laura Waters, Andrea Gritz, Desmond Maitland,
• Brian Gazzard Mark Nelson.
• Research Fellow PKR/SSR
• St. Stephens Centre
• Chelsea Westminster Hospital, London.

2
Introduction

• Guidelines recommend 3 fixed dose NRTI
  combinations for initial therapy
• - Tenofovir emtricitabine
• - Abacavir lamivudine
• - Zidovudine lamivudine
• Combivir less attractive due to twice-daily
  dosing and probable association with lipoatrophy.

ABC
3
Introduction

• Adverse events are a common cause of treatment
  discontinuation1,2
• ABC HSR occurs in 5-8 individuals3,4
• Strong association between ABC HSR and HLA B5701
  positivity5,6
• Prospective testing has reduced ABC HSR in two
  cohorts. 7,8

1. Monforte et al 2000 2. OBrien et al 2003 3.
European SPC 4. US SPC 5. Mallal et al 2002
6. Hetherington et al 2002 7. Rauch et al
2006 8. Reeves et al 2006.
4
Fall in early ABC discontinuation with genetic
screening
Possible ABC-related symptoms
Beforegenetic screening
Aftergenetic screening
Definite ABC HSR 2 patients results not
reviewed prior to therapy 1 patient with
informed choice/incomplete haplotype
Proportion of ABC-naïve patients discontinuing
ABC within 6 weeks
plt0.05


1998/1999
2000/2001
2002/2003
20047/2005
n68
n131
n107
n60
Rauch A et al 2006.
5
Fall in early ABC discontinuation with genetic
screening
Possible ABC-related symptoms
Beforegenetic screening
Aftergenetic screening
Definite ABC HSR 2 patients results not
reviewed prior to therapy 1 patient with
informed choice/incomplete haplotype
Proportion of ABC-naïve patients discontinuing
ABC within 6 weeks
plt0.05


1998/1999
2000/2001
2002/2003
20047/2005
n68
n131
n102
n49
Rauch A et al 2006.
6
Clinician assessed HSR pre and post-B5701
350
300
p 0.001
250
Number of subjects
200
total
150
6.2 (4.1-9.4)
HSR
100
0.5 (0.1-3.0)
50
0
Pre B5701
Post B5701
Reeves I et al. ADRL 2006
7
Aims

• To describe the frequency of the HLA B5701
  allele in our clinic cohort
• To assess the rate of ABC discontinuation with
  prospective HLA testing
• To compare ABC HSR rates before and after the
  introduction of routine HLA B5701 screening.

8
Methods

• HLA screening was introduced in August 2005 for
• - all treatment-naïve subjects commencing
  therapy
• - treatment-experienced patients considering a
  switch to ABC
• ABC avoided if B5701 positive
• All individuals undergoing HLA testing between
  1/8/05 and 1/7/06 were reviewed.

9
Methods

• Data collected - gender, ethnicity
• - treatment history
• - adverse events
• Detailed case note review of all subjects
  discontinuing ABC
• Suspected ABC HSR rate with prospective B5701
  screening compared with historical ABC HSR rate
  (1/8/04 1/8/05).

10
Statistical Methods

• ABC HSR rates before and after the use of
  prospective HLA B5701 testing
  Chi-squared test with Yates correction.
• ABC HSR rates between groups
  Chi-squared test with Yates correction or
  Fishers exact test.

11
Results

• 739 HLA B5701 tests performed
• - 735 successful
• - 4 test failures
• 54/735 tested HLA B5701 positive 7.3
• 11/111 females HLA B5701 positive 9.9
• 43/624 males HLA B5701 positive 6.9

p-value 0.35, Yates Correction
12
Results
13
Results
14
Results
15
B5701- Suspected HSR
SPP Skin Patch Testing
16
Suspected HSR Pre Post Prospective B5701
Testing
201
p 0.10
200
Starting ABC
180
160
Suspected HSR
134
140
120
Number individuals
100
3.0
7.5
80
60
40
10
6
20
0
Pre-B5701 testing
Pre-B5701 testing
17
Suspected HSR Pre Post Prospective B5701
Testing
199
p 0.03
200
Starting ABC
180
160
Suspected HSR
134
140
120
Number individuals
100
2.0
7.5
80
60
40
10
4
20
0
Pre-B5701 testing
Pre-B5701 testing
18
ABC HSR Rates in Treatment-Naïve Experienced
Subjects
p 0.57
151
160
Starting ABC
140
Suspected HSR
120
100
80
2.6
60
47
40
20
4
0
0
Naïve individuals
Experienced individuals
by Fishers exact test
19
Conclusions

• The introduction of prospective HLA B5701
  screening reduced the incidence of ABC HSR in our
  cohort.
• Despite testing HLA B5701 negative, 4
  individuals (2.0) discontinued ABC for suspected
  HSR.

20
Conclusions

• 1 HLA B5701 negative subject developed HSR with
  a positive SPT and systemic symptoms.
• Our data highlight the importance of maintaining
  clinical vigilance when prescribing ABC
  regardless of the HLA B5701 result.

21
Acknowledgements

• Sundhiya Mandalia
• Marta Boffito
• St Stephens Centre staff patients