长效HIV疗法应用于存在依从性挑战的非洲成人
完整摘要 · 中文译文
背景：在东部和南部非洲，约有100万接受口服治疗的人类免疫缺陷病毒（HIV）感染者因依从性挑战而未实现病毒抑制。 方法：我们开展了一项3b期、开放标签、随机试验，在病毒学抑制的HIV-1（病毒载量<200拷贝/毫升）且依从性或照护参与欠佳的成人中，比较长效注射用卡博特韦加利匹韦林与基于多替拉韦的口服治疗。参与者按1:1比例分配接受每8周一次肌肉注射卡博特韦（600 mg）加利匹韦林（900 mg）（前两次注射就诊间隔4周），或继续每日口服基于多替拉韦的治疗；未进行基线耐药检测。主要终点为第48周时病毒载量<50拷贝/毫升；非劣效性以-10个百分点为界值进行评估。确认病毒学失败（连续两次病毒载量≥200拷贝/毫升）是关键次要终点。 结果：共在肯尼亚、南非和乌干达的7个研究中心入组了540名受试者；其中537名被纳入主要分析。第48周时，长效治疗组268名受试者中有244名（91.0%）的病毒载量低于50拷贝/毫升，而口服治疗组269名受试者中有240名（89.2%）（风险差异为1.9个百分点；95%置信区间（CI）为-3.1至6.9），符合非劣效性标准。符合方案分析的结果与主要分析结果一致。长效治疗组有5名受试者（1.9%）发生确认病毒学失败，口服治疗组无受试者发生（风险差异为1.9个百分点；95% CI为0.3至3.5）。接受长效治疗的271名受试者中有11名（4.1%）和接受口服治疗的269名受试者中有8名（3.0%）报告了严重不良事件（风险差异为1.1个百分点；95% CI为-1.1至4.2）。 结论：在非洲存在依从性困难的HIV感染者中，长效卡博特韦联合利匹韦林在维持病毒载量低于50拷贝/毫升方面不劣于基于口服多替拉韦的治疗。（由强生公司资助；IMPALA的ClinicalTrials.gov注册号为NCT05546242；泛非临床试验注册号为PACT202301600757432TMC278LAHTX3005）。
完整摘要 · 英文原文
BACKGROUND: In eastern and southern Africa, approximately 1 million people living with human immunodeficiency virus (HIV) and receiving oral therapy do not have viral suppression because of 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. 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. 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. Confirmed virologic failure (two consecutive viral loads of ≥200 copies per milliliter) was a key secondary end point. RESULTS: A total of 540 participants were enrolled across seven sites in Kenya, South Africa, and Uganda; 537 were included in the primary analysis. 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. The results of a per-protocol analysis were consistent with those of the primary analysis. 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). 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). 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. (Funded by Johnson & Johnson; IMPALA ClinicalTrials.gov number, NCT05546242; Pan African Clinical Trials Registry number, PACT202301600757432TMC278LAHTX3005.).