Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment.

Long-acting oral-drug combinations could offer new options with less frequent dose administration.

长效口服药物组合可能提供新的选择，减少剂量的频繁给药。

Methods

We conducted a phase 3, double-blind, randomized, active-controlled, noninferiority trial in 12 countries to evaluate the efficacy and safety of a switch to once-weekly oral islatravir-lenacapavir (ISL/LEN) from once-daily oral bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) in adults in whom HIV-1 had been virologically suppressed for at least 6 months while they were receiving B/F/TAF.

我们在12个国家进行了一项3期、双盲、随机、活性对照、非劣效试验，以评估从每日一次口服bictegravir-emtricitabine-tenofovir alafenamide（B/F/TAF）转换为每周一次口服islatravir-lenacapavir（ISL/LEN）的有效性和安全性，这是在患者接受B/F/TAF治疗至少6个月并且HIV-1病毒学抑制的情况下进行的。

Participants were assigned in a 1:1 ratio to receive once-weekly ISL/LEN (2 mg/300 mg) or to continue once-daily B/F/TAF for 96 weeks; all received matched placebo for the alternative regimen.

参与者以1:1的比例被分配接受每周一次的ISL/LEN（2毫克/300毫克）或继续每日一次的B/F/TAF治疗96周；所有人都接受了替代方案的匹配安慰剂。

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, as determined by the Food and Drug Administration-defined snapshot algorithm.

主要终点是48周时HIV-1 RNA水平达到或超过50拷贝/毫升的参与者百分比，这是由美国食品药品监督管理局定义的快照算法确定的。

Noninferiority was determined at a margin of 4 percentage points.

非劣效性是在4个百分点的边界上确定的。

Results

A total of 607 participants underwent randomization; 304 were assigned to the ISL/LEN group and 303 to the B/F/TAF group.

共有607名参与者进行了随机分组；304人被分配到ISL/LEN组，303人被分配到B/F/TAF组。

A total of 21% of the participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were 65 years of age or older.

总共有21%的参与者是女性，31%是黑人，26%是西班牙裔或拉丁裔，15%是65岁或以上。

At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was reported in no participants in the ISL/LEN group and 1 (0.3%) in the B/F/TAF group (difference, -0.3 percentage points; 95.002% confidence interval[CI], -1.4 to 0.8); an HIV-1 RNA level of less than 50 copies per milliliter was reported in 284 (93.4%) and 280 (92.4%), respectively (difference, 1.0 percentage point, 95% CI, -3.2 to 5.2).

在第48周，ISL/LEN组中没有参与者报告HIV-1 RNA水平达到或超过50拷贝/毫升，而在B/F/TAF组中有1名（0.3%）（差异，-0.3个百分点；95.002%置信区间[CI]，-1.4到0.8）；HIV-1 RNA水平低于50拷贝/毫升分别报告了284名（93.4%）和280名（92.4%）（差异，1.0个百分点，95% CI，-3.2到5.2）。

The mean change in the CD4+ T-cell count at week 48 was -10 cells per microliter with ISL/LEN and -18 cells per microliter with B/F/TAF (least-squares mean difference, 12 cells per microliter; 95% CI, -16 to 39).

在第48周，CD4+ T细胞计数的平均变化为ISL/LEN组每微升减少10个细胞，B/F/TAF组每微升减少18个细胞（最小二乘均值差异，每微升12个细胞；95% CI，-16到39）。

The trial regimen was discontinued owing to adverse events in 6 participants (2.0%) in the ISL/LEN group and 5 (1.7%) in the B/F/TAF group; serious adverse events occurred in 16 (5.3%) and 14 (4.6%), respectively.

由于不良事件，有6名（2.0%）ISL/LEN组的参与者和5名（1.7%）B/F/TAF组的参与者停止了试验方案；分别有16名（5.3%）和14名（4.6%）发生了严重不良事件。

Conclusions

Among persons with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF in maintaining HIV viral load suppression.

在HIV-1病毒学抑制人群中，每周一次口服的ISL/LEN在维持HIV病毒载量抑制方面与每日一次的B/F/TAF相当。

(Funded by Gilead Sciences and Merck Sharp and Dohme; ISLEND-1 ClinicalTrials.gov number, NCT06630286.).

(该试验由Gilead Sciences和Merck Sharp and Dohme资助；ISLEND-1 ClinicalTrials.gov编号，NCT06630286。)