Background Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control. Methods The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated. Results We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. Conclusions This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers. Clinical Trials Registration NCT04553081.

中文翻译：

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对 HIV 宿主的深入分析证实了多替拉韦/拉米夫定在 4 期随机对照转换试验 （RUMBA） 中的有效性和安全性


背景减少终身人类免疫缺陷病毒 （HIV） 治疗的活性化合物数量是有益的，尤其是为了减少潜在的长期副作用。到目前为止，评估病毒对照的现有数据支持 2DR（2 药物方案）抗逆转录病毒疗法与 3DR 相比的稳健性和安全性。然而，必须对病毒库进行进一步深入的研究，以保证这些方案在稳定完整的 HIV-1 DNA 拷贝、HIV-1 RNA 转录物和持续免疫控制方面的长期安全性。方法 RUMBA 研究是第一个评估从 3DR 转换为 2DR 对病毒库影响的前瞻性随机对照试验。使用 HIV-1 RNA < 50 拷贝/mL 血浆的任何稳定的第二代整合酶链转移抑制剂 3DR 方案至少 3 个月的参与者被随机分配至多替拉韦/拉米夫定 （DTG/3TC，n = 89） 或改用或继续使用比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺 （B/F/TAF，n = 45）。48 周后，评估病毒学、免疫学和代谢参数。结果与 B/F/TAF 相比，DTG/3TC 未观察到完整 HIV-1 DNA 拷贝/百万 CD4+ T 细胞的平均数量随时间变化的显著差异。本研究中没有证据表明改用 DTG/3TC 会通过 HIV-1 转录增加活性储存库。未观察到促炎细胞因子或主要免疫细胞亚群的显着变化。特定细胞亚群的耗竭和激活的变化很小且是双向的。治疗方案之间的代谢结局相似。 结论 在深入研究完整的 HIV-1 储存库、HIV-1 转录和炎症标志物后，本研究通过病毒控制证实了 DTG/3TC 与 B/F/TAF 相比的安全性。临床试验注册 NCT04553081.