HLA-B*35 is associated with nevirapine hypersensitivity in the contemporary western australian HIV cohort study
Phillips, E., Lucas, M., Keane, N., Lucas, A., McKinnon, E. and Mallal, S. (2010) HLA-B*35 is associated with nevirapine hypersensitivity in the contemporary western australian HIV cohort study. In: 4th International Drug Hypersensitivity Meeting, 22 - 25 April 2010, Rome, Italy.
Background: Treatment with the antiretroviral nevirapine is complicated by a hypersensitivity syndrome (NVP HSR) in approximately 5% of those starting the drug. Previous studies have suggested associations with both Class I and Class II major histocompatibility complex alleles suggesting that the immunopathogenesis and pharmacogenetics of this reaction may vary. Prior to 2005 we had described an association between nevirapine rash associated hepatitis and the HLA class II allele DRB1*0101 in predominantly Caucasian men with CD4+%>25% and more recently a Thai group has described an association between HLA-B*3505 and nevirapine rash and HSR. Material and Methods: Patients in the Western Australian Cohort study who had received nevirapine and were tolerant for at least 3 months or who had developed NVP HSR were identified. NVP HSR was defined as a minimum of fever and at least one of hepatitis and rash. Co-variates examined included CD4+ count and viral load at commencement of nevirapine treatment, age, gender, viral load, hepatitis C status, and HLA Class I and II alleles. Nevirapine ELISpot to the parent drug and its 12-OH metabolite was performed on consenting patients when stored PBMCs were available. Results: Of 401 patients exposed to NVP between March 1993 and November 2009, 15 (3.7%) were identified who met criteria for NVP HSR. 10/15 (67%) patients were White and 5/15 (33%) Asian origin. 8/15 (53%) of patients had a combination of both fever and eosinophilia and at least one of hepatitis and rash. Factors significantly associated with NVP HSR included HLA-B*35 [OR 4.4, p=0.016]. There was no association between NVP HSR and CD4+ count at treatment although in patients exposed to nevirapine mean CD4+ count at treatment was higher > 2005 versus < 2004 (517 + 308 vs. 433 + 277 p=0.014). Of the 6/15 patients with cells available for nevirapine ELISpot, 2 patients (33%) were positive with both sharing the haplotype HLA-A*2407-B*35-C*0401. Conclusions: The changing epidemiology and ethnicity of our population with more recent cases of NVP HSR occurring in those of Southeast Asian and Indonesian background is a potential explanation for the association between HLA-B*35 and NVP HSR and the current lack of association between pre-treatment CD4+ count and NVP HSR in our cohort.
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|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
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