Publication: HLA-B* 3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients
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Issued Date
2009
Resource Type
File Type
application/pdf
ISSN
17446872
Other identifier(s)
2-s2.0-59549096348
Rights Holder(s)
Scopus
Bibliographic Citation
Pharmacogenetics and Genomics. Vol 19, No.2 (2009), p.139-146
Suggested Citation
Chantarangsu S., Mushiroda T., Mahasirimongkol S., Kiertiburanakul S., Sungkanuparph S., Manosuthi W., Tantisiriwat W., Charoenyingwattana A., Sura T., Chantratita W., Nakamura Y. HLA-B* 3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients. Pharmacogenetics and Genomics. Vol 19, No.2 (2009), p.139-146. doi:10.1097/FPC.0b013e32831d0faf Retrieved from: https://hdl.handle.net/20.500.14740/7635
Abstract
Objective Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-mduced skin rash among HIV-infected patients. Methods A step-wise case-control association study was conducted. The first set of samples consisted of 80 samples from patients with NVP-induced skin rash and 80 samples from NVP-tolerant patients. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. Subsequently, we verified HLA alleles that showed a possible association in the first screening using an additional set of samples consisting of 67 cases with NVP-induced skin rash and 105 controls. Results An HLA-B*3505 allele revealed a significant association with NVP-induced skin rash in the first and second screenings. In the combined data set, the HLA-B*3505 allele was observed in 17.5% of the patients with NVP-induced skin rash compared with only 1.1% observed in NVP-tolerant patients [odds ratio (OR) = 18.96; 95% confidence interval (Cl)=4.87-73.44, Pc=4.6 × 10 -6] and 0.7% in general Thai population (OR = 29.87; 95% Cl = 5.04-175.86, Pc=2.6 × 10 -5). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% Cl = 6.45-374.41, P= 0.00017). Conclusion A strong association between the HLA-B*3505 and NVP-induced skin rash provides a novel insight into the pathogenesis of drug-induced rash in the HIV-infected population. On account of its high specificity (98.9%) in identifying NVP-induced rash, it is possible to utilize the HLA-B*3505 as a marker to avoid a subset of NVP-induced rash, at least in Thai population. © 2009 Wolters Kluwer Health| Lippincott Williams & Wilkins.
Subject(s)
HLA B antigen
Nevirapine
Anti human immunodeficiency virus agent
Adult
Allele
Article
Controlled study
Drug tolerance
Female
Genotype
HLA system
Human
Human immunodeficiency virus infection
Logistic regression analysis
Major clinical study
Male
Pharmacogenetics
Predictor variable
Priority journal
Rash
Sensitivity and specificity
Thailand
Allele
Case control study
Chemically induced disorder
Genetics
Human immunodeficiency virus infection
Pathology
Rash
Adult
Alleles
Anti-HIV Agents
Case-Control Studies
Exanthema
Female
Genotype
HIV Infections
HLA-B Antigens
Humans
Male
Nevirapine
Thailand
Nevirapine
Anti human immunodeficiency virus agent
Adult
Allele
Article
Controlled study
Drug tolerance
Female
Genotype
HLA system
Human
Human immunodeficiency virus infection
Logistic regression analysis
Major clinical study
Male
Pharmacogenetics
Predictor variable
Priority journal
Rash
Sensitivity and specificity
Thailand
Allele
Case control study
Chemically induced disorder
Genetics
Human immunodeficiency virus infection
Pathology
Rash
Adult
Alleles
Anti-HIV Agents
Case-Control Studies
Exanthema
Female
Genotype
HIV Infections
HLA-B Antigens
Humans
Male
Nevirapine
Thailand