Background

Simplified antiretroviral therapy (ART) regimens are desirable for people with HIV. We investigated the efficacy and safety of switching from triple ART to dual dolutegravir plus lamivudine therapy.

Methods

DOLAM is a phase 4, randomised, open-label, non-inferiority trial, done at six HIV clinics in Catalonia, Spain. Adults with HIV-1 receiving a triple ART regimen, aged 18 years or older, with virological suppression, a CD4 nadir of at least 200 cells per μL, who were HBsAg-negative, and without previous viral failure or resistance mutations to study drugs were eligible. Participants underwent computer-generated randomisation, stratified by the class of the third drug, and were assigned (1:1) to switch to oral dolutegravir 50 mg and lamivudine 300 mg once daily or to continue triple ART for 48 weeks. The primary endpoint was the proportion of people with an HIV RNA value of at least 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm, 8% non-inferiority margin). Both the primary and safety outcomes were evaluated in the intention-to-treat exposed population. The study is completed and was registered with EudraCT 201500027435.

Findings

Between July 7, 2015, and Oct 31, 2018, 265 participants were randomly assigned to switch to dolutegravir plus lamivudine (n=131) or to maintain triple ART (n=134) and all received at least one dose. Nine (7%) participants in the dual therapy group and ten (7%) in the triple therapy group were excluded before 48 weeks, mostly due to treatment discontinuations or virological failure. Participants were predominantly male (116 [87%] of 134 in the triple ART group and 111 [85%] of 131 in the dolutegravir plus lamivudine group). The difference in the proportion of participants with HIV RNA values of at least 50 copies per mL at 48 weeks between the dual therapy group (three [2%] of 131) and triple therapy group (two [1%] of 134) was 0·8 percentage points (95% CI –3·3 to 5·2), showing non-inferiority of dolutegravir plus lamivudine dual therapy compared with triple ART. 73 (56%) of 131 participants allocated to dual therapy had 150 adverse effects, compared with 78 (58%) of 134 participants allocated to triple therapy who also had 150 adverse events (p=0·68). Drug discontinuation due to adverse effects occurred in four people in the triple therapy group and three people in the dual therapy group.

Interpretation

Our findings show the efficacy and safety of dolutegravir plus lamivudine as a simplified therapy switch option for selected people with HIV with virological suppression on triple ART.

Funding

Instituto de Salud Carlos III, Red de Investigación en Sida, and ViiV Healthcare.

中文翻译：

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48 周时病毒学抑制的 HIV 成人患者改用多替拉韦加拉米夫定与继续三联抗逆转录病毒治疗的疗效和安全性 (DOLAM)：一项随机非劣效性试验

背景

HIV 感染者需要简化的抗逆转录病毒疗法 (ART) 方案。我们调查了从三联 ART 转换为双多替拉韦加拉米夫定治疗的有效性和安全性。

方法

DOLAM 是一项 4 期、随机、开放标签、非劣效性试验，在西班牙加泰罗尼亚的六家 HIV 诊所进行。接受三联 ART 方案的 HIV-1 成人、18 岁或以上、病毒学抑制、CD4 最低点至少为每微升 200 个细胞、HBsAg 阴性、以前没有病毒失败或对研究药物的耐药性突变是符合条件。参与者接受了计算机生成的随机化，按第三种药物的类别进行分层，并被分配 (1:1) 改为口服多替拉韦 50 毫克和拉米夫定 300 毫克，每天一次或继续三联 ART 持续 48 周。主要终点是在第 48 周时 HIV RNA 值至少为每毫升 50 拷贝的人群比例（美国食品和药物管理局快照算法，8% 的非劣效性边际）。在意向治疗暴露人群中评估了主要结局和安全性结局。该研究已完成并已在 EudraCT 201500027435 注册。

调查结果

2015 年 7 月 7 日至 2018 年 10 月 31 日期间，265 名参与者被随机分配改用多替拉韦加拉米夫定（n=131）或维持三联 ART（n=134），并且所有参与者都至少接受了一剂。在 48 周之前，双重治疗组的九名 (7%) 参与者和三联疗法组的十名 (7%) 参与者被排除在外，主要是由于治疗中断或病毒学失败。参与者主要是男性（三联 ART 组 134 人中的 116 人 [87%] 和多替拉韦加拉米夫定组 131 人中的 111 人 [85%]）。双重治疗组（131 人中的 3 个 [2%]）和 134 人中的 2 个 [1%]）在 48 周时 HIV RNA 值至少为每毫升 50 拷贝的参与者比例差异为 0 ·8 个百分点（95% CI –3·3 到 5·2），显示与三联 ART 相比，多替拉韦加拉米夫定双重治疗的非劣效性。分配给双联疗法的 131 名参与者中有 73 名 (56%) 有 150 次不良反应，而分配到三联疗法的 134 名参与者中有 78 名 (58%) 也有 150 次不良事件 (p=0·68)。三联疗法组 4 人和双联疗法组 3 人因不良反应停药。

口译

我们的研究结果显示了多替拉韦加拉米夫定作为一种简化的治疗转换选择的有效性和安全性，适用于对三重 ART 进行病毒学抑制的特定 HIV 感染者。

资金

Instituto de Salud Carlos III、Red de Investigación en Sida 和 ViiV Healthcare。