HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients.
OBJECTIVE
Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-induced 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 (CI)=4.87-73.44, Pc=4.6x10] and 0.7% in general Thai population (OR=29.87; 95% CI=5.04-175.86, Pc=2.6x10). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% CI=6.45-374.41, P=0.00017).


CONCLUSIONS
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.
Chantarangsu
Soranun
S
Research Group for Pharmacogenomics, RIKEN, Center for Genomic Medicine, Tokyo, Japan.
Mushiroda
Taisei
T
Mahasirimongkol
Surakameth
S
Kiertiburanakul
Sasisopin
S
Sungkanuparph
Somnuek
S
Manosuthi
Weerawat
W
Tantisiriwat
Woraphot
W
Charoenyingwattana
Angkana
A
Sura
Thanyachai
T
Chantratita
Wasun
W
Nakamura
Yusuke
Y
D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005076:Exanthema / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D013785:Thailand
D019380:Anti-HIV Agents; D015235:HLA-B Antigens; D019829:Nevirapine