Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population.
Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population.
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DOI：
10.1093/cid/cit021
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Pirmohamed M
中科院分区：
文献类型：
--
作者：
Carr DF;Chaponda M;Jorgensen AL;Castro EC;van Oosterhout JJ;Khoo SH;Lalloo DG;Heyderman RS;Alfirevic A;Pirmohamed M
272名接受奈韦拉平治疗方案的马拉维HIV患者（其中117人对奈韦拉平过敏）的人类白细胞抗原基因分型显示，HLA-C*04:01增加Stevens-Johnson综合征/中毒性表皮坏死松解的风险，优势比为5.17（95%可信区间为2.39-11.18）。背景。在许多撒哈拉以南非洲国家，非核苷类逆转录酶抑制剂奈韦拉平是治疗人类免疫缺陷病毒（HIV）的基石。然而，奈韦拉平与发生不同表型的过敏反应的6%-10%的风险相关，包括起泡条件史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解（TEN）。我们的目的是鉴定与奈韦拉平过敏相关的预测性人类白细胞抗原（HLA）标记物。方法。我们确定了117名hiv感染的马拉维成年人奈韦拉平过敏（15名药物性肝损伤[DILI]， 33名SJS/TEN， 20名过敏综合征，46名奈韦拉平引起的皮疹，3名同时患有DILI和SJS表型）和155名年龄、性别和种族匹配的奈韦拉平暴露对照组。采用基于序列的高分辨率方案对5个基因座（A、B、C、DRB1和DQB1）进行HLA分型。Logistic回归分析将CD4+细胞计数作为协变量。结果。在二元logistic回归模型中，与基线罕见等位基因组相比，HLA-C*04:01显著增加SJS（优势比[OR] = 17.52； 95%可信区间为3.31-92.80）和所有超敏表型（OR = 2.64; 95% CI, 1.13-6.18）的风险。携带HLA-C*04:01相关的SJS/TEN绝对风险OR为5.17 （95% CI, 2.39-11.18）。阳性预测值为2.6%，阴性预测值为99.2%。此外，HLA-DQB1基因座内的许多等位基因可防止奈韦拉平诱导的超敏表型。结论。我们的研究已经确定HLA-C*04:01携带是奈韦拉平诱导的SJS/TEN在马拉维HIV队列中的一个危险因素。需要在更大的患者队列中验证这些发现，并对发病机制进行机制研究。
Human leukocyte antigen genotyping of 272 Malawian HIV patients receiving nevirapine-containing regimens (of whom 117 had nevirapine hypersensitivity) has shown that HLA-C*04:01 increases the risk of Stevens-Johnson syndrome/toxic epidermal necrolysis, with an odds ratio of 5.17 (95% confidence interval, 2.39–11.18). Background. The nonnucleoside reverse transcriptase inhibitor nevirapine is the cornerstone of treatment for human immunodeficiency virus (HIV) in many sub-Saharan African countries. However, nevirapine is associated with a 6%–10% risk of developing a hypersensitivity reaction, with different phenotypes, including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte antigen (HLA) markers that are associated with nevirapine hypersensitivity. Methods. We identified 117 HIV-infected Malawian adults with nevirapine hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex- and ethnicity-matched nevirapine-exposed controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a sequence-based high-resolution protocol. Logistic regression analysis included CD4+ cell count as a covariate. Results. HLA-C*04:01 was found to markedly increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 3.31–92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13–6.18) when compared to the baseline rare allele group in a binary logistic regression model. The OR for absolute risk of SJS/TEN associated with carriage of HLA-C*04:01 was 5.17 (95% CI, 2.39–11.18). Positive predictive value was 2.6% and negative predictive value was 99.2%. In addition, a number of alleles within the HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes. Conclusions. Our study has identified HLA-C*04:01 carriage as a risk factor for nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings in a larger cohort of patients and mechanistic investigation of the pathogenesis are required.
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影响因子：
3.8
作者：
Littera, Roberto;Carcassi, Carlo;Manconi, Paolo Emilio
通讯作者：
Manconi, Paolo Emilio
DOI：
10.1073/pnas.0409500102
发表时间：
2005-03-15
影响因子：
11.1
作者：
Hung, SL;Chung, WH;Chen, YT
通讯作者：
Chen, YT
影响因子：
3
作者：
Penzak, S. R.;Kabuye, G.;Masur, H.
通讯作者：
Masur, H.
影响因子：
9.3
作者：
De Maat, MMR;Mathôt, RAA;Beijnen, JH
通讯作者：
Beijnen, JH
影响因子：
158.5
作者：
Mallal, Simon;Phillips, Elizabeth;Benbow, Alastair
通讯作者：
Benbow, Alastair