Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Clin Pharmacol Ther. 2019 Aug;106(2):450-457. doi: 10.1002/cpt.1403. Epub 2019 Mar 29.
Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The aim of this study was to assess the influence of single-nucleotide polymorphisms (SNPs) in genes encoding for proteins involved in antitubercular drug disposition or effect. A pharmacogenetic study was conducted in Kampala, Uganda, where all analysis was performed. The impact of SNPs on antitubercular drug exposure, adverse events, and treatment outcomes was evaluated in patients coinfected with HIV/TB receiving treatments for both conditions. In 221 participants, N-acetyltransferase 2 (NAT2; rs1799930), solute carrier organic anion transporter family member 1B1 (SLCO1B1; rs4149032), and pregnane X receptor (PXR; rs2472677) variants affected isoniazid exposure in multivariate analysis. Most patients were deemed cured (163; 73.8%), yet PXR 63396TT carriers had a higher probability of death (P = 0.007) and of worsening peripheral neuropathy (P = 0.018). In this exploratory study in Ugandan patients coinfected with HIV/TB, genetic variants in PXR, SLCO1B1, and NAT2 were moderately associated with isoniazid exposure, whereas PXR 63396TT carriers showed worse outcomes.
在同时感染 HIV 和结核病（TB）的患者中，治疗结果并不理想。本研究旨在评估参与抗结核药物处置或效应的蛋白编码基因中的单核苷酸多态性（SNPs）的影响。在乌干达坎帕拉进行了一项遗传药理学研究，所有分析均在此进行。在接受两种疾病治疗的同时感染 HIV/TB 的患者中，评估了 SNPs 对抗结核药物暴露、不良事件和治疗结果的影响。在 221 名参与者中，N-乙酰转移酶 2（NAT2；rs1799930）、溶质载体有机阴离子转运蛋白家族成员 1B1（SLCO1B1；rs4149032）和妊娠相关 X 受体（PXR；rs2472677）变体在多变量分析中影响异烟肼的暴露。大多数患者被认为治愈（163；73.8%），但 PXR 63396TT 携带者的死亡（P = 0.007）和周围神经病变恶化的可能性更高（P = 0.018）。在这项对乌干达同时感染 HIV/TB 的患者进行的探索性研究中，PXR、SLCO1B1 和 NAT2 的遗传变异与异烟肼暴露中度相关，而 PXR 63396TT 携带者的预后更差。
