Background

Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection.

Methods

We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir–abacavir–lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm).

Results

At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, −0.4 percentage points; 95% confidence interval [CI], −2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, −3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, −10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48.

Conclusions

Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir–abacavir–lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.)

中文翻译：

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口服诱导HIV-1感染后长效卡博格韦和利非韦林

背景

长效注射方案可简化1型人类免疫缺陷病毒（HIV-1）感染患者的治疗。

方法

我们进行了一项3期随机开放标签试验，其中曾经接受过dolutegravir–abacavir–lamivudine的未曾接受抗逆转录病毒治疗的HIV-1感染的成年人每天口服诱导治疗20周。在16周后，将HIV-1 RNA水平低于每毫升50拷贝的参与者随机分配（1：1）继续进行当前的口服治疗，或改用口服Cabotegravir加rilpivirine治疗1个月，然后每月长期注射代理Cabotegravir加rilpivirine。主要终点是在第48周时，HIV-1 RNA水平为每毫升50拷贝或更高的参与者的百分比（食品和药物管理局快照算法）。

结果

在第48周，接受长效治疗的283名参与者中有6名（2.1％）和接受口服治疗的283名（7％）中有7名（2.5％）的HIV-1 RNA水平达到每毫升50拷贝或更高，-0.4个百分点； 95％的置信区间[CI]，-2.8至2.1），该结果符合主要终点的非劣效性标准（利润率为6个百分点）。在第48周时，接受长效治疗的93.6％和接受口服治疗的93.3％的HIV-1 RNA水平低于每毫升50拷贝（校正差异，0.4个百分点； 95％CI，-3.7至4.5），该结果符合该终点的非劣等标准（利润率为-10个百分点）。在接受长效治疗的参与者中，有86％报告了注射部位反应（中位持续时间为3天；轻度或中度严重程度，占99％）；由于注射相关原因，有4名参与者退出了试验。接受长效治疗的11％和2％的患者发生3级或更高级别的不良事件和符合肝相关停止标准的事件，而接受口服治疗的发生率分别为3％和4％和1％。参与者改用长效治疗后，治疗满意度提高；在第48周，有91％的人选择长效治疗。

结论

就维持HIV-1抑制作用而言，长效卡博可韦+利培韦林的治疗不逊于dolutegravir–abacavir–lamivudine的口服治疗。注射部位反应很常见。（由ViiV Healthcare和Janssen资助； FLAIR ClinicalTrials.gov编号，NCT02938520。）