From the University of Nebraska Medical Center, Omaha (S.S.); Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Mexico (J.-F.A.-V.); Broward Health Medical Center, Broward Health Imperial Point, Fort Lauderdale, FL (G.J.R.); Fatebenefratelli Sacco Hospital, Milan (G.R.); the Center for Infectious Diseases, Berlin (A.B.); Hospital de Elche, Elche, Spain (M.M.); Maxwell Centre, Durban, South Africa (G.L.); the Central Research Institute of Epidemiology, Moscow (V.P.); Metropolis Medical Group, San Francisco (F.B.); Maple Leaf Research, Toronto (G.S.), and GlaxoSmithKline, Mississauga (J.H.) - both in Ontario, Canada; Fundación Huésped, Buenos Aires (P.C.); Chungnam National University School of Medicine, Daejeon, South Korea (Y.-S.K.); GlaxoSmithKline (S.L.F.) and ViiV Healthcare (C.L.T., P.P., J.M., C.M.H., K.J.H., D.A.M., K.Y.S., W.R.S.) - both in Research Triangle Park, NC; ViiV Healthcare, Brentford, United Kingdom (V.C.); and Janssen Research and Development, Beerse, Belgium (H.C., W.P., S.V., P.E.W.).
N Engl J Med. 2020 Mar 19;382(12):1112-1123. doi: 10.1056/NEJMoa1904398. Epub 2020 Mar 4.
Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.
In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. 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, determined with the use of the Food and Drug Administration snapshot algorithm.
Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.
Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).
简化的人类免疫缺陷病毒 1 型（HIV-1）感染治疗方案可能会提高患者的满意度并促进治疗依从性。
在这项涉及 308 名参与者的 3 期、开放性标签、多中心非劣效性试验中，参与者在接受标准口服抗逆转录病毒治疗时，血浆 HIV-1 RNA 水平已低于 50 拷贝/毫升至少 6 个月，我们将参与者随机分配（1:1）继续接受口服治疗或转换为每月一次的长效卡替拉韦、HIV-1 整合酶链转移抑制剂和长效利匹韦林、非核苷类逆转录酶抑制剂肌内注射。主要终点是第 48 周时 HIV-1 RNA 水平为 50 拷贝/毫升或更高的参与者比例，采用食品和药物管理局快照算法确定。
每组有 308 名参与者开始治疗。第 48 周时，长效治疗组有 5 名（1.6%）和口服治疗组有 3 名（1.0%）参与者的 HIV-1 RNA 水平为 50 拷贝/毫升或更高（调整差异，0.6 个百分点；95%置信区间[CI]，-1.2 至 2.5），该结果符合主要终点非劣效性标准（非劣效性边界，6 个百分点）。长效治疗组有 92.5%和口服治疗组有 95.5%的参与者在第 48 周时 HIV-1 RNA 水平低于 50 拷贝/毫升（调整差异，-3.0 个百分点；95%CI，-6.7 至 0.7），该结果符合该终点的非劣效性标准（非劣效性边界，-10 个百分点）。长效治疗组有 3 名参与者和口服治疗组有 4 名参与者确认发生病毒学失败。长效治疗组更常见与注射相关的不良事件，包括注射部位疼痛，在 231 名（75%）长效治疗组接受者中发生，大多数情况下为轻度或中度；1%的患者因该事件退出。每个治疗组均有不超过 5%的参与者报告严重不良事件。
长效卡替拉韦和利匹韦林每月注射与标准口服治疗在维持 HIV-1 抑制方面非劣效。与注射相关的不良事件很常见，但很少导致停药。（由 ViiV Healthcare 和杨森资助；ATLAS ClinicalTrials.gov 编号，NCT02951052）。
