Islatravir：一种首创的核苷类逆转录酶易位抑制剂，用于HIV治疗。
完整摘要 · 中文译文
综述目的：Islatravir是首创的核苷类逆转录酶易位抑制剂（NRTTI），以高抗病毒效力和长细胞内半衰期为特征。近期临床进展——包括在先前观察到的淋巴细胞减少后进行剂量优化、每日一次多拉韦林/Islatravir的3期评价，以及每周一次Islatravir/来那卡帕韦联合疗法的开发——有必要重新评估其在HIV治疗中的潜在作用。 近期发现：近期3期研究显示，多拉韦林/Islatravir 100/0.25 mg在从已确立的抗逆转录病毒治疗转换后维持病毒学抑制，且总淋巴细胞或CD4+ T细胞计数无临床意义的降低。这些发现支持降低Islatravir暴露量的有效性和安全性。该方案在初治个体中也不劣于比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺。两项3期转换试验进一步显示，在研的Islatravir/来那卡帕韦（2 mg/300 mg）可通过每周一次口服给药维持病毒学抑制。耐药性研究确定M184I/V是影响Islatravir敏感性的主要途径。 总结：Islatravir将新颖的作用机制与药理学特性相结合，使简化和延长间隔的治疗成为可能。其未来的重要性可能超越每日治疗，通过促进有效的每周一次口服抗逆转录病毒治疗而延伸。
完整摘要 · 英文原文
PURPOSE OF REVIEW: Islatravir is a first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTTI) characterized by high antiviral potency and a long intracellular half-life. Recent clinical developments, including dose optimization following previously observed lymphocyte reductions, phase 3 evaluation of once-daily doravirine/islatravir, and development of once-weekly islatravir/lenacapavir combination therapy, warrant reassessment of its potential role in HIV treatment. RECENT FINDINGS: Recent phase 3 studies show that doravirine/islatravir 100/0.25 mg maintains virologic suppression after switching from established antiretroviral therapy, without clinically meaningful reductions in total lymphocyte or CD4+ T-cell counts. These findings support the efficacy and safety of reduced islatravir exposure. The regimen was also noninferior to bictegravir/emtricitabine/tenofovir alafenamide in treatment-naïve individuals. Two phase 3 switch trials further showed that investigational islatravir/lenacapavir (2 mg/300 mg) can maintain virologic suppression with once-weekly oral dosing. Resistance studies identify M184I/V as the principal pathway affecting islatravir susceptibility. SUMMARY: Islatravir combines a novel mechanism of action with pharmacologic properties enabling simplified and extended-interval treatment. Its future importance may extend beyond daily therapy by facilitating effective once-weekly oral antiretroviral treatment.