BACKGROUND Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV. METHODS We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group). Participants in the exposed group were matched 1:2 to individuals continuing stable non-doravirine-containing ART, on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4-count, pre-ART plasma viral load (PVL) and anchor drug class before switching. The primary outcome was protocol-defined virological failure (PDVF; PVL of ≥200 copies per mL) in the intention-to-treat (ITT) population at week 104, with participants modifying their regimen or becoming lost to follow-up considered as PDVF (non-inferiority margin +5%). In contrast, in the on-treatment population, those who modified their regimen or became lost to follow-up were censored from that moment onwards. Tolerability was a secondary outcome. FINDINGS In total, 590 participants in the exposed group and 1180 participants in the unexposed group (of whom 55·3% used integrase strand transfer inhibitor-based regimens) were included. In the ITT analysis, PDVF occurred in 135 (22·9%) exposed participants and in 295 (25·0%) unexposed participants (risk difference -2·12%, upper limit of the one-sided 95% CI +1·40%). In the on-treatment analysis, 10 (2·2%) of 455 non-censored exposed participants and 26 (2·9%) of 885 non-censored unexposed participants had PDVF (risk difference -0·70%, upper limit of the one-sided 95% CI +0·73%). All exposed participants with a PVL of 200 copies or more per mL resuppressed without regimen modification: no confirmed virological failure (two consecutive PVLs of ≥200 copies per mL) was observed. 104 (17·6%) exposed participants and 211 (17·9%) unexposed participants modified their regimen. 73 (12.4%) exposed participants discontinued doravirine due to adverse events: abnormal dreams (1·7%) and insomnia (1·5%) were most common. INTERPRETATION Switching to doravirine in well suppressed people with HIV without previous virological failure was non-inferior compared with continuing non-doravirine-containing regimens after 2 years in a real-world setting. FUNDING None.

中文翻译：

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HIV 感染者改用基于多拉韦林的抗逆转录病毒疗法的真实有效性和耐受性：一项全国性、匹配的前瞻性队列研究。


背景技术目前，关于多拉韦林的真实数据很少。在一项全国前瞻性队列中，我们评估了 HIV 感染者改用基于多拉韦林的抗逆转录病毒疗法 (ART) 的有效性和耐受性。方法 我们对之前没有病毒学失败且在 2020 年 9 月 1 日之前转用多拉韦林（暴露组）的不含多拉韦林的三联或双联 ART 治疗稳定至少 12 个月的 HIV 感染者进行了一项全国性匹配的前瞻性队列研究。暴露组的参与者与继续稳定的不含多拉韦林的 ART 的个体进行 1:2 匹配，包括年龄、性别、HIV 感染类别、ART 开始后的时间、日历时间、ART 前 CD4 计数、ART 前血浆病毒切换前的负荷 (PVL) 和锚定药物类别。主要结局是第 104 周时意向治疗 (ITT) 人群出现方案定义的病毒学失败（PDVF；PVL ≥200 拷贝/mL），参与者修改其治疗方案或失访被视为 PDVF （非劣效裕度+5%）。相比之下，在接受治疗的人群中，那些改变治疗方案或失去随访的人从那一刻起就受到审查。耐受性是次要结果。结果 总共包括 590 名暴露组参与者和 1180 名未暴露组参与者（其中 55·3% 使用基于整合酶链转移抑制剂的方案）。在 ITT 分析中，135 名 (22·9%) 暴露参与者和 295 名 (25·0%) 未暴露参与者发生 PDVF（风险差异 -2·12%，单侧 95% CI +1·上限） 40%）。 在治疗分析中，455 名未经审查的暴露参与者中的 10 名 (2·2%) 和 885 名未经审查的未暴露参与者中的 26 名 (2·9%) 患有 PDVF（风险差异 -0·70%，上限为单侧 95% CI +0·73%）。所有 PVL 为 200 拷贝/mL 或以上的暴露参与者均在未修改方案的情况下重新抑制：未观察到确认的病毒学失败（两次连续 PVL ≥ 200 拷贝/mL）。 104 名 (17·6%) 暴露参与者和 211 名 (17·9%) 未暴露参与者修改了他们的治疗方案。 73 名（12.4%）暴露参与者因不良事件而停用多拉韦林：最常见的是异常梦境（1·7%）和失眠（1·5%）。解释 在现实环境中，对于未曾发生病毒学失败且受到良好抑制的 HIV 感染者来说，与持续使用不含多拉韦林的治疗方案 2 年后相比，改用多拉韦林并不逊色。资金 无。