Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA 30307, USA.
Viruses. 2022 May 31;14(6):1202. doi: 10.3390/v14061202.
Long-acting (LA) anti-HIV regimens show promise for increasing dosing intervals and consequently, improving the patients' quality of life. The first FDA-approved LA therapy is Cabenuva, which comprises rilpivirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (integrase strand transfer inhibitor). Novel promising LA anti-HIV agents such as lenacapavir (a capsid-targeting antiviral) and islatravir (EFdA, a nucleoside reverse transcriptase translocation inhibitor) need to be explored as combination therapies. Therefore, we sought to determine whether combination of lenacapavir with islatravir, rilpivirine, or cabotegravir displayed synergy, additivity, or antagonism. We performed dose-response matrices of these drug combinations in an HIV-1 reporter cell line and subsequently analyzed the data with SynergyFinder Plus, which employs four major drug interaction models: highest single agent, Bliss independence, Loewe additivity, and zero interaction potency. Most of these models predict additive inhibition by the studied drug combinations This work highlights the importance of effective drug combinations in LA-regimens.
长效（LA）抗 HIV 方案有望增加给药间隔，从而提高患者的生活质量。首个获得 FDA 批准的 LA 疗法是卡布韦（Cabenuva），它由利匹韦林（一种非核苷类逆转录酶抑制剂）和卡替拉韦（整合酶链转移抑制剂）组成。新型有前途的 LA 抗 HIV 药物，如 lenacapavir（一种衣壳靶向抗病毒药物）和伊拉特拉韦（EFdA，一种核苷类逆转录酶易位抑制剂），需要作为联合疗法进行探索。因此，我们试图确定 lenacapavir 与伊拉特拉韦、利匹韦林或卡替拉韦联合使用是否具有协同作用、相加作用或拮抗作用。我们在 HIV-1 报告细胞系中进行了这些药物组合的剂量反应矩阵实验，随后使用 SynergyFinder Plus 分析数据，该软件采用了四种主要的药物相互作用模型：最高单药、Bliss 独立性、Loewe 相加性和零相互作用效力。这些模型中的大多数预测了研究药物组合的相加抑制作用。这项工作强调了在 LA 方案中使用有效药物组合的重要性。
