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在结核病/艾滋病毒患者中,药基因组学关联与HIV-1病毒抑制

Felipe Ridolfi¹, Gustavo Amorim¹, David W Haas¹

¹Vanderbilt University Medical Center.

Research square

|January 7, 2025

概括

遗传变异没有显著影响结核病/艾滋病毒患者的抗逆转录病毒治疗 (ART) 结果. 这项研究发现病毒抑制率低,特定基因变异与治疗成功之间没有明确的联系.

科学领域:

药物基因组学药物基因组学
传染性疾病传染性疾病
免疫学免疫学免疫学

背景情况:

人类遗传变异影响药物代谢,可能导致结核病 (TB) 和人类免疫缺陷病毒 (HIV) 患者的毒性或治疗失败.
了解这些遗传因素对于优化共感染个体的抗逆转录病毒疗法 (ART) 至关重要.

研究的目的:

研究结核病/艾滋病毒共感染患者药物代谢酶的遗传变异与HIV-1病毒抑制结果之间的关联.
在这个人群中,比较基于非核糖逆转录酶抑制剂 (NNRTI) 和基于整合酶链转移抑制剂 (INSTI) 的ART疗法的有效性.

主要方法:

分析了来自RePORT-巴西研究的194名结核病/艾滋病毒患者的队列,这些患者开始接受标准结核病治疗和ART.
基因定型集中在CYP2B6 (rs3745274,rs28399499,rs4803419) 和UGT1A1 (rs887829) 变体上,这些变体已知会影响埃法维伦兹,多卢特格拉维尔和拉尔特格拉维尔的代谢.
评估了HIV-1病毒抑制,并使用费舍尔测试和生存分析对ART疗法和不同基因型组之间的结果进行了比较.

主要成果:

总体而言,病毒抑制是次优的 (68%),在基于NNRTI (efavirenz) 和基于INSTI (raltegravir) 的ART疗法之间,抑制率或抑制时间没有显著差异.
在CYP2B6或UGT1A1基因型与实现病毒抑制的可能性或时间之间没有发现显著的关联.
在没有实现抑制的参与者中,在 efavirenz 和 INSTI 组中都观察到共同的基因型.

结论:

在这个观察队列中,影响ART代谢的遗传变异与结核病/艾滋病毒患者的病毒抑制结果没有显著的关联.
病毒抑制率低,凸显了对影响这种复杂患者群体治疗疗效的其他因素的进一步研究的需要.

关键词:

艾滋病毒-1 治疗治疗结核病/艾滋病毒遗传多形态的遗传多形态.药物遗传学药物遗传学病毒学抑制病毒学抑制

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