Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00839-19. Print 2019 Oct.
Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant ( > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration () below the proposed target of 3.0 mg/liter ( = 0.03). In multivariate analysis, anti-TB therapy and the 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean and area under the drug concentration-time curve from time zero to 12 h (AUC) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.).
基于奈韦拉平的抗逆转录病毒疗法（ART）是合并结核分枝杆菌（TB）感染的 3 岁以下 HIV 感染儿童（幼儿）的有限选择之一。迄今为止，尚无足够的数据推荐幼儿在一线抗结核（抗-TB）治疗期间使用基于奈韦拉平的治疗。我们比较了合并 TB 感染和未合并 TB 感染的 HIV 感染幼儿奈韦拉平的药代动力学（PK）。在合并组中，在抗-TB 治疗期间和完成抗-TB 治疗方案后评估奈韦拉平 PK。在 53 名参与者中，23 名（43%）有 TB-HIV 合并感染。尽管两组之间奈韦拉平 PK 参数的平均差异无统计学意义（>0.05），但 23 名 TB-HIV 合并感染儿童中有 14 名（61%）和 30 名 HIV 感染儿童中有 9 名（30%）的奈韦拉平最小浓度（）低于建议的 3.0mg/L 目标（=0.03）。在多变量分析中，抗-TB 治疗和 516G>T 基因型是奈韦拉平 PK 参数的共同预测因子。在 516GG 基因型的儿童中，两组间奈韦拉平 PK 参数的差异有统计学意义，但 GT 或 TT 基因型无统计学意义。在 14 名有配对数据的 TB-HIV 合并感染参与者中，当患者接受抗-TB 治疗时，奈韦拉平的几何平均浓度（）和从 0 至 12 小时的药物浓度-时间曲线下面积（AUC）约低 34%，而奈韦拉平表观口服清除率（CL/）约高 45%。虽然本研究中抗-TB 治疗对奈韦拉平 PK 的诱导作用适度，但 TB 药物方案效应的 基因型依赖性变异性将使合并 TB-HIV 感染的幼儿的任何剂量调整策略复杂化。需要在该年龄组中更能与 TB 治疗相兼容的替代 ART 方案。（本研究已在 ClinicalTrials.gov 注册，标识符为 NCT01699633。）
