Background

Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.

Methods

In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm.

Results

Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], −1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, −3.0 percentage points; 95% CI, −6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, −10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting–therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.

Conclusions

Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.)

VISUAL ABSTRACT
Long-Acting Cabotegravir and Rilpivirine for HIV-1

中文翻译：

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长效卡博格拉韦和利吡韦林用于维持HIV-1抑制

背景

治疗1型人类免疫缺陷病毒（HIV-1）感染的简化方案可能会提高患者满意度并促进依从性。

方法

在这个第三阶段，开放性，多中心，非劣效性试验中，在接受标准口服抗逆转录病毒治疗的同时，血浆HIV-1 RNA水平低于每毫升50拷贝的患者至少6个月的患者，我们随机分配了参与者（1： 1）继续口服治疗或转为每月一次肌肉注射长效卡博韦韦（一种HIV-1整合酶链转移抑制剂）和长效瑞比韦林（一种非核苷类逆转录酶抑制剂）。主要终点是使用食品药品监督管理局快照算法确定的，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。

结果

每组308名参与者开始治疗。在第48周，在接受长效治疗的5位参与者（1.6％）和接受口服治疗的3位参与者（1.0％）中发现了每毫升50拷贝或更高的HIV-1 RNA水平（校正差，0.6个百分点； 95％）置信区间[CI]为-1.2到2.5），该结果符合主要终点的非劣效标准（非劣效容限，6个百分点）。在第48周时，接受长效治疗的参与者中有92.5％和接受口服治疗的参与者中95.5％的HIV-1 RNA水平低于每毫升50个拷贝（调整后差异为-3.0个百分点； CI为95％， -6.7到0.7），该结果符合该终点的非劣效性标准（劣势裕度，-10个百分点）。在接受长效治疗的3名参与者和接受口服治疗的4名参与者中确认了病毒学衰竭。长效治疗组的不良事件更为常见，包括注射部位疼痛，长效治疗的231例接受者（占75％）发生不良反应，在大多数情况下为轻度或中度。1％的人因为此事件而退出。据报道，每组中不超过5％的参与者发生了严重的不良事件。

结论

每月长效卡博可韦和利比韦林的注射均不逊于维持HIV-1抑制的标准口服疗法。注射相关的不良事件很常见，但很少导致停药。（由ViiV Healthcare和Janssen资助； ATLAS ClinicalTrials.gov编号，NCT02951052。）

视觉摘要
长效卡博韦韦和利吡韦林治疗HIV-1