Long-Acting HIV Therapy in African Adults with Adherence Challenges.

Methods

We conducted a phase 3b, open-label, randomized trial to compare long-acting injectable cabotegravir plus rilpivirine with oral dolutegravir-based therapy among adults with virally suppressed HIV type 1 (viral load, <200 copies per milliliter) and suboptimal adherence or care engagement.

我们进行了一项3b期、开放标签、随机试验，比较了长效注射卡博特韦加利匹韦林与基于多替拉韦的口服治疗，针对的是病毒抑制的HIV-1成人（病毒载量<200拷贝/毫升）和依从性或关怀参与度不佳的情况。

The participants were assigned in a 1:1 ratio to receive intramuscular injections of cabotegravir (600 mg) plus rilpivirine (900 mg) every 8 weeks, with the first two injection visits occurring 4 weeks apart, or to continue daily oral dolutegravir-based therapy; baseline drug-resistance testing was not performed.

参与者按1:1的比例分配，接受每8周一次的卡博特韦（600毫克）加利匹韦林（900毫克）肌肉注射，前两次注射间隔4周，或继续每天服用基于多替拉韦的口服治疗；未进行基线药物耐药性测试。

The primary end point was a viral load of less than 50 copies per milliliter at week 48; noninferiority was assessed with a margin of -10 percentage points.

主要终点是在第48周时病毒载量低于50拷贝/毫升；通过-10个百分点的边界评估非劣效性。

Confirmed virologic failure (two consecutive viral loads of ≥200 copies per milliliter) was a key secondary end point.

确认的病毒学失败（连续两次病毒载量≥200拷贝/毫升）是一个关键的次要终点。

Results

A total of 540 participants were enrolled across seven sites in Kenya, South Africa, and Uganda; 537 were included in the primary analysis.

共有540名参与者在肯尼亚、南非和乌干达的七个地点被纳入研究；537名参与者被纳入主要分析。

At 48 weeks, 244 of 268 participants (91.0%) in the long-acting-therapy group had a viral load of less than 50 copies per milliliter, as compared with 240 of 269 participants (89.2%) in the oral-therapy group (risk difference, 1.9 percentage points; 95% confidence interval[CI], -3.1 to 6.9), which met the criterion for noninferiority.

在48周时，长效治疗组的268名参与者中有244名（91.0%）的病毒载量低于50拷贝/毫升，而口服治疗组的269名参与者中有240名（89.2%）的病毒载量低于50拷贝/毫升（风险差异，1.9个百分点；95%置信区间[CI]，-3.1至6.9），这满足了非劣效性的标准。

The results of a per-protocol analysis were consistent with those of the primary analysis.

按方案分析的结果与主要分析的结果一致。

Confirmed virologic failure occurred in 5 participants (1.9%) in the long-acting-therapy group and in no participants in the oral-therapy group (risk difference, 1.9 percentage points; 95% CI, 0.3 to 3.5).

在长效治疗组中，有5名参与者（1.9%）发生了确认的病毒学失败，而在口服治疗组中没有参与者发生病毒学失败（风险差异，1.9个百分点；95%置信区间，0.3至3.5）。

Serious adverse events were reported in 11 of 271 participants (4.1%) who received long-acting therapy and in 8 of 269 participants (3.0%) who received oral therapy (risk difference, 1.1 percentage points; 95% CI, -1.1 to 4.2).

在接受长效治疗的271名参与者中，有11人（4.1%）报告了严重不良事件，在接受口服治疗的269名参与者中，有8人（3.0%）报告了严重不良事件（风险差异，1.1个百分点；95%置信区间，-1.1至4.2）。

Conclusions

Among persons with HIV in Africa who have adherence challenges, long-acting cabotegravir plus rilpivirine was noninferior to oral dolutegravir-based therapy for maintaining a viral load of less than 50 copies per milliliter.

在非洲有HIV并面临依从性挑战的人群中，长效卡博特韦加利匹韦林与口服多替拉韦为基础的治疗在维持每毫升少于50个拷贝的病毒载量方面非劣效。

(Funded by Johnson & Johnson; IMPALA ClinicalTrials.gov number, NCT05546242; Pan African Clinical Trials Registry number, PACT202301600757432TMC278LAHTX3005.).

该项目由强生公司资助；IMPALA ClinicalTrials.gov编号为NCT05546242；泛非临床试验注册编号为PACT202301600757432TMC278LAHTX3005。