在一项4期随机对照转换试验（RUMBA）中，对HIV储存库的深入分析证实了多替拉韦/拉米夫定的有效性和安全性。
In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA).
作者信息
De Scheerder Marie-Angélique, Degroote Sophie, Delporte Mareva, Kiselinova Maja, Trypsteen Wim, Vincke Lara, De Smet Evelien, Van Den Eeckhout Bram, Schrooyen Loïc, Verschoore Maxime, Muccini Camilla, Vanherrewege Sophie, Caluwe Els, De Buyser Stefanie, Gerlo Sarah, Blomme Evy, Vandekerckhove Linos
机构信息
Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
出版信息
J Infect Dis. 2025 Feb 4;231(1):e91-e100. doi: 10.1093/infdis/jiae405.
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.
背景
减少用于人类免疫缺陷病毒（HIV）终身治疗的活性化合物数量备受关注，特别是为了减少潜在的长期副作用。到目前为止，评估病毒控制的现有数据支持与三联抗逆转录病毒疗法（3DR）相比，二联抗逆转录病毒疗法（2DR）的稳健性和安全性。然而，必须对病毒储存库进行进一步深入研究，以确保这些疗法在稳定完整的HIV-1 DNA拷贝、HIV-1 RNA转录本和持续免疫控制方面的长期安全性。
方法
RUMBA研究是第一项前瞻性随机对照试验，评估从3DR转换为2DR对病毒储存库的影响。至少3个月血浆HIV-1 RNA<50拷贝/mL且采用任何基于第二代整合酶链转移抑制剂的稳定3DR方案的参与者被随机分为两组，一组转换为多替拉韦/拉米夫定（DTG/3TC，n = 89），另一组转换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，我们未观察到DTG/3TC治疗的每百万CD4+ T细胞中完整HIV-1 DNA拷贝平均数随时间的变化有显著差异。本研究没有证据表明转换为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有显著变化。特定细胞亚群的耗竭和激活变化很小且呈双向。两种治疗方案的代谢结果相似。
结论
通过对完整HIV-1储存库、HIV-1转录和炎症标志物进行深入研究，本研究证实了与B/F/TAF相比，DTG/3TC的安全性。
临床试验注册
NCT04553081。
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