Introduction The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters. Methods Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (1:1) to switch to 2DR or to continue 3DR for 48 weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48 weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms. Results Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (48:0). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR. Conclusions Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.

中文翻译：

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从三联抗逆转录病毒疗法转为多替拉韦加拉米夫定的多组学血浆效应

简介 DOLAM 试验显示，经过 48 周的随访，从三联抗逆转录病毒疗法（三种药物方案；3DR）改为多替拉韦加拉米夫定（两种药物方案；2DR）在病毒学上并不劣于持续 3DR。相对于 3DR，2DR 的体重有所增加，但对代谢参数没有影响。方法进行多组学血浆分析，以进一步了解这种治疗转换是否可能影响特定的生物途径。 DOLAM (EudraCT 201500027435) 是一项 4 期、随机、开放标签、非劣效性试验，其中接受 3DR 治疗的病毒学抑制的 HIV 患者被分配 (1:1) 转为 2DR 或继续 3DR 48 周。在基线和 48 周时进行了非靶向蛋白质组学、代谢组学和脂质组学分析。进行单变量和多变量分析以确定两个治疗组之间关键分子的变化。结果从 3DR 切换到 2DR 显示对 N-乙酰胞壁酰-L-丙氨酸酰胺酶 (Q96PD5)、胰岛素样生长因子结合蛋白 3 (A6XND0)、丙氨酸和甘油三酯 (TG) 的循环血浆浓度产生多组学影响 (48:0 ）。相关性分析确定了接受 2DR 治疗的人中这四种分子的上调之间的关联。结论 非靶向多组学分析研究确定了可能与炎症免疫途径以及脂质和葡萄糖代谢相关的分子变化。尽管这些变化可能与潜在的代谢或心血管后果有关，但其临床意义仍不确定。需要进一步的工作来证实这些发现并评估其长期临床后果。