HLA-B* 3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients

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.