Diapositiva 1

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Use of HCP5-single nucleotide polymorphism to
predict abacavir hypersensitivity reactions -
Correlation with HLA-B5701
Sonia Rodriguez-Novoa1, Lorena Cuenca1, Judit
Morello1, Mateo Córdoba2, Francisco Blanco2,
Inmaculada Jiménez-Nácher1 and Vincent
Soriano2 1Pharmacokinetic Unit and 2Infectious
Diseases Department Hospital Carlos III, Madrid,
Spain
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Introduction

• Abacavir potent and convenient (qd).
• Adverse effect abacavir hypersensitivity
  reaction.
• 5-8 of patients.
• Within first 6 weeks.
• Symptoms fever, rash, malaise, diarrhea and
  respiratory alterations.
• Recovery after stopping ABC.
• Re-challenging severe recurrence of symptoms
  with increased risk of life-threatening
  complications and death.

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Risk factors associated with ABC HSR
DR7, DQ3, HLA-B5701
MHC-III
MHC-II
MHC-I
DR
DQ
DP
HLA-B
HLA-A
HLA-C
HLA-B5701Abacavir-HSR
PREDICT-1
Clinically diagnosed HSR PPV 61
NPV 95
Mallal S, et al. 2008
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HLA-B5701 carriage frequency
West EUROPE 5-7
MIDDLE EAST 1-2 (NB 5-7 Ashkenazi Jews)
MEDITERRANEAN 1-2
UK 8
US Caucasian 8
INDIA 5-20
CHINA 0 (NB 2.5 N.E. provinces)
US Asian 1
JAPAN 0
US African-American 2.5
THAILAND 4-10
AUSTRALIA 8
US Hispanic 2
THAILAND B57 carriage 3- 11
S. AMERICAN Caucasian 5-7
Sub-Saharan AFRICA lt1
Nolan et al, J HIV Ther 2003 8(2)36-41
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Methodologies for HLA-B5701 testing (I)

• Serological methods
• Cytometry
• Molecular biology techniques
• Sequencing
• PCR-SSO
• PCR-SSP

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Methodologies for HLA-B5701 testing (II)

• New genetic marker a polymorphism located
  within the HLA complex P5 gene, HCP5 rs2395029.
• It is in high linkage disequilibrium with
  HLA-B5701.

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Objective
To examine the correlation between HLA-B5701 and
HCP5 rs2395029 in a relatively large HIV
population.
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Patients Methods
Patients

• HIV patients ABC-naïve were prospectively
  screened for HLA-B5701 prior to starting ABC.

Methods

• DNA was extracted from whole blood.
• HCP5 rs2395029 genotyping allelic
  discrimination (TaqMan 5-nuclease assay).
• High resolution HLA class I typing SSP HLA DNA
  typing.

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Results
HLA-B5701 positive 14 patients
HCP5 positive 15 patients
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Correlation between HCP5 and HLA-B5701
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Clinical outcome
245 patients
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Conclusions

• Good correlation between HCP5 rs2395029 and
  HLA-B5701 (NPV100) ? HCP5 good tool to avoid
  the ABC HSR in clinical settings.
• HCP5 screening is easier and cheaper ? replace
  HLA-B5701 testing to prevent the ABC HSR.
• Future studies are necessary to confirm these
  results in larger and ethnically more diverse HIV
  populations.

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Acknowledgments
Clinical Team Francisco Blanco Mateo
Córdoba Pablo Barreiro Pablo Labarga José
Medrano Eugenia Vispo Luz Martín-Carbonero Juan
González-Lahoz Vicente Soriano
Pharmacology Lab Sonia Rodríguez Nóvoa Lorena
Cuenca Elena Álvarez Gema González
Pardo Inmaculada Jiménez