Tuberculosis Research Centre (Indian Council of Medical Research), Chennai, India.
J Antimicrob Chemother. 2011 Jun;66(6):1354-9. doi: 10.1093/jac/dkr075. Epub 2011 Mar 9.
Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression.
To study the influence of age, drug dose and formulation type, nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs.
A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels.
Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (P < 0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (P < 0.01). Children ≤ 3 years had a 3.2 (95% confidence interval 1.07-9.45) times higher risk of having sub-therapeutic nevirapine concentrations.
Nevirapine blood concentrations are affected by many factors, most notably age ≤ 3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings.
奈韦拉平是儿科联合抗 HIV 治疗的重要组成部分。为了实现持久的病毒抑制，需要有足够的药物暴露。
研究年龄、药物剂量和剂型、营养状况和 CYP2B6 516G>T 多态性对接受仿制药抗逆转录病毒药物治疗的儿童奈韦拉平血药浓度的影响。
在印度的四个地点进行了一项多中心研究。招募了接受通用奈韦拉平固定剂量联合制剂治疗的 HIV 感染儿童。采用 HPLC 测定奈韦拉平的谷值和 2 小时奈韦拉平血浆浓度。采用直接测序法对 CYP2B6 基因多态性进行了特征描述。记录临床和营养状况。使用 Mann-Whitney U 检验比较组间差异，采用多变量逻辑回归分析确定导致低药物水平的因素。
研究了 94 名中位年龄为 78 个月的儿童；60%存在营养不良或发育迟缓。与非发育迟缓儿童相比，发育迟缓儿童的 2 小时奈韦拉平浓度明显较低（P < 0.05）；不同营养组之间的谷浓度没有显著差异。与 GG 和 GT CYP2B6 基因型相比，TT 基因型儿童的奈韦拉平水平显著升高（P < 0.01）。≤ 3 岁的儿童发生奈韦拉平治疗浓度不足的风险高 3.2 倍（95%置信区间 1.07-9.45）。
奈韦拉平的血药浓度受多种因素影响，尤其是年龄≤3 岁；年龄较小、发育迟缓以及 CYP2B6 GG 或 GT 基因型的组合可能导致奈韦拉平治疗浓度不足。应根据这些发现重新审查儿童的用药建议。
