Switch to injectable cabotegravir-rilpivirine given every 8 weeks in adolescents living with HIV with virological suppression in sub-Saharan Africa (LATA): a randomised, open-label, multicentre, 96-week non-inferiority trial.

We evaluated efficacy and safety of LAI cabotegravir-rilpivirine compared with daily oral ART in adolescents living with HIV with virological suppression in Africa.

我们评估了长效注射卡博特韦-利匹韦林与每日口服抗逆转录病毒治疗（ART）在非洲HIV携带青少年中的疗效和安全性，这些青少年已经实现了病毒学抑制。

Methods

LATA, a randomised, open-label, multicentre, non-inferiority trial, recruited adolescents with HIV aged from 12 years to younger than 20 years from five clinics in Kenya, South Africa, Uganda, and Zimbabwe.

LATA是一项随机、开放标签、多中心、非劣效试验，招募了来自肯尼亚、南非、乌干达和津巴布韦五家诊所的12岁至不到20岁的HIV携带青少年。

Participants had to have virological suppression (HIV-1 viral load <50 copies per mL) for more than 12 months and no previous treatment failure.

参与者必须实现病毒学抑制（HIV-1病毒载量<50拷贝/毫升）超过12个月，且无先前治疗失败。

Participants were randomly assigned (1:1) to receive either LAI cabotegravir-rilpivirine (LAI group) or daily oral dolutegravir-lamivudine-tenofovir disoproxil fumarate (TLD; control group).

参与者被随机分配（1:1）接受长效注射卡博特韦-利匹韦林（LAI组）或每日口服多替拉韦-拉米夫定-替诺福韦二丙酸酯（TLD；对照组）。

Randomisation was stratified by clinical centre and mode of infection (vertical vs horizontal or other).

随机化按临床中心和感染方式（垂直vs水平或其他）进行分层。

Participants, clinical staff, and researchers were unmasked to treatment allocation, whereas laboratory staff measuring viral loads were masked.

参与者、临床工作人员和研究人员对治疗分配不知情，而测量病毒载量的实验室工作人员则不知情。

Participants in the LAI group were assigned to receive cabotegravir (600 mg)-rilpivirine (900 mg) intramuscular injections at weeks 4, 8, 16, and every 8 weeks thereafter.

LAI组的参与者被分配在第4周、第8周、第16周以及此后每8周接受一次卡博特韦（600毫克）-利匹韦林（900毫克）肌肉注射。

Participants in the control group were assigned to receive the oral fixed-dose combination, dolutegravir (50 mg)-lamivudine (300 mg)-tenofovir disoproxil fumarate (300 mg), every day.

对照组的参与者被分配每天口服固定剂量组合，多替拉韦（50毫克）-拉米夫定（300毫克）-替诺福韦二吡呋酯（300毫克）。

Viral loads were measured every 24 weeks.

病毒载量每24周测量一次。

The primary outcome was the proportion of participants with two consecutive (confirmed) viral load measurements equal to or higher than 50 copies per mL by week 96, estimated using adjusted Kaplan-Meier methods, by intention to treat.

主要结果是到第96周时，参与者中有连续两次（确认的）病毒载量测量结果等于或高于50拷贝/毫升的比例，使用调整的Kaplan-Meier方法估计，按治疗意向分析。

The non-inferiority margin and confidence level depended on the control event rate (8·9% margin, 99% CI, for 6% event rate).

非劣效性边界和置信水平取决于对照事件率（对于6%的事件率，非劣效性边界为8.9%，置信区间为99%）。

If non-inferiority was demonstrated, superiority was assessed at the α=5% level.

如果证明了非劣效性，则在α=5%的水平上评估优越性。

This trial is completed and registered with ClinicalTrials.gov, NCT05154747.

这项试验已经完成，并在ClinicalTrials.gov上注册，注册号为NCT05154747。

Results

Between June 22, 2023, and April 15, 2024, 476 of 560 screened adolescents with HIV were enrolled in LATA and randomly assigned to either the LAI group (n=235) or the control group (n=241).

在2023年6月22日至2024年4月15日期间，共有560名筛查出的HIV青少年中有476名被纳入LATA研究，并随机分配到LAI组（n=235）或对照组（n=241）。

Of the 476 randomised participants, 466 (98%) had acquired HIV vertically, and 200 (42%) were recruited from Uganda, 128 (27%) from Zimbabwe, 77 (16%) from Kenya, and 71 (15%) from South Africa.

在476名随机分配的参与者中，有466名（98%）是通过垂直传播获得HIV的，有200名（42%）来自乌干达，128名（27%）来自津巴布韦，77名（16%）来自肯尼亚，71名（15%）来自南非。

Median age was 16·5 years (IQR 14·8-18·1), 256 (54%) participants were female, 220 (46%) were male, 474 (>99%) were Black, and median duration of previous ART was 11·7 years (IQR 8·5-14·1).

中位年龄为16.5岁（四分位数间距14.8-18.1），256名（54%）参与者为女性，220名（46%）为男性，474名（>99%）为黑人，之前抗逆转录病毒治疗的中位持续时间为11.7年（四分位数间距8.5-14.1）。

Median follow-up was 120 weeks (IQR 104-128).

中位随访时间为120周（四分位数间距104-128）。

Two participants in the LAI group had confirmed viral load of 50 copies per mL or higher by week 96 (Kaplan-Meier estimated proportion 0·9%, 95% CI 0·0 to 2·2) versus 15 participants (6·4%, 3·7 to 9·8) in the control group (estimated difference -5·5%, 99% CI -10·3 to -1·5).

在LAI组中，有两名参与者在第96周时确认病毒载量为50拷贝/毫升或更高（Kaplan-Meier估计比例为0.9%，95%置信区间0.0至2.2），而在对照组中有15名参与者（6.4%，3.7至9.8）（估计差异为-5.5%，99%置信区间-10.3至-1.5）。

LAI met the non-inferiority criterion and demonstrated superiority over control (p=0·0013).

LAI达到了非劣效性标准，并显示出优于对照组的优越性（p=0.0013）。

By the end of follow-up, seven participants permanently discontinued LAI (one confirmed viral load ≥200 copies per mL, two LAI-related adverse events [serious hypersensitivity reaction; non-serious drug eruption], one incident tuberculosis, two planning pregnancy, and one participant choice).

随访结束时，有七名参与者永久停止使用LAI（一名确认病毒载量≥200拷贝/毫升，两名与LAI相关的不良事件[严重过敏反应；非严重药物疹]，一例结核病，两例计划怀孕，以及一名参与者的选择）。

There were 14 serious adverse events (in 14 participants) in the LAI group, including one homicide, compared with 18 (in 12 participants) in the control group, including one death from metastatic osteosarcoma (hazard ratio[HR] 1·16, 95% CI 0·54 to 2·51; p=0·71).

LAI组中有14例严重不良事件（涉及14名参与者），包括一例凶杀案，而在对照组中有18例（涉及12名参与者），包括一例因转移性骨肉瘤死亡（风险比[HR] 1.16，95%置信区间0.54至2.51；p=0.71）。

The only treatment-related serious adverse eventwas hypersensitivity reaction.

唯一与治疗相关的严重不良事件是过敏反应。

There were 31 adverse events of grade 3 or higher (in 27 participants) in the LAI group and 34 (in 26 participants) in the control group (HR 1·07, 0·62 to 1·83; 0·81).

LAI组中有31例3级或更高级别的不良事件（涉及27名参与者），而对照组中有34例（涉及26名参与者）（HR 1.07，0.62至1.83；0.81）。

These events included four injection-site reactions (in the LAI group); otherwise, adverse eventprofiles were similar between trial groups.

这些事件包括四例注射部位反应（在LAI组中）；否则，试验组之间的不良事件特征相似。

interpretation

In adolescents with HIV with virological suppression, LAI cabotegravir-rilpivirine was superior to TLD for maintaining virological suppression, with no new safety concerns observed.

在HIV阳性的青少年中，如果病毒学抑制得到维持，LAI卡博特格韦-利匹韦林比TLD更有效，且未观察到新的安全问题。

These findings support LAI cabotegravir-rilpivirine as a maintenance treatment option for this population.

这些发现支持将LAI卡博特格韦-利匹韦林作为这一人群的维持治疗选择。

funding

European and Developing Countries Clinical Trials Partnership (EDCTP2), Janssen, UK Medical Research Council.

欧洲和开发中国家临床试验伙伴关系（EDCTP2）、杨森、英国医学研究委员会。