多替拉韦作为儿童 HIV-1 感染的一线或二线治疗药物。
Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.
机构信息
From the Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology (A.T., E.W., S.A., T.S., B.W., C.S., D.F., D.M.G.), the University College London Great Ormond Street Institute of Child Health (N.K.), and the Department of Global Health and Development, London School of Hygiene and Tropical Medicine (S.B.), London, and Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham (S.B.W.) - all in the United Kingdom; the University of Zimbabwe, Harare (H.A.M., M.B.-D., G.M.); Baylor College of Medicine, Fort Portal (A.R.K., P.A., D.B.), the Joint Clinical Research Center, Mbarara (A. Lugemwa, S.M., L.A.), and the Joint Clinical Research Center (C.M.K., E.K., V.M.), Makerere University-Johns Hopkins University Research Collaboration (P.M., L.B.-M., G.M.A.), and Makerere University (V.M.), Kampala - all in Uganda; the Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg (A.V., N.R., E.V., A. Liberty), the Family Centre for Research with Ubuntu, the Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg (M.F.C.), the Department of Paediatrics and Children Health, King Edward VIII Hospital, University of KwaZulu-Natal (M.A.), and the Africa Health Research Institute (O.B., N.K.), Durban - all in South Africa; the Program for HIV Prevention and Treatment-Institut de Recherche pour le Développement Research Unit, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai (T.R.C., S.C.), the Faculty of Medicine, Chulalongkorn University (T.P.), and HIV-NAT (HIV Netherlands Australia Thailand Research Collaboration), Thai Red Cross AIDS Research Center, Bangkok (T.P.), and Prapokklao Hospital, Chanthaburi (C.N.) - all in Thailand; the First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.); the Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (A. Colbers); the School of Public Health, University of Sydney, Sydney (S.B.); INSERM-ANRS SC10-US019, Essais Thérapeutiques et Maladies Infectieuses, Villejuif, France (Y.S., A. Coelho, A. Compagnucci); the Penta Foundation (T.G., C.G.), and the Department of Women and Child Health, University of Padua (C.G.) - both in Padua, Italy; and the Pediatric Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Madrid (P.R.).
出版信息
N Engl J Med. 2021 Dec 30;385(27):2531-2543. doi: 10.1056/NEJMoa2108793.
BACKGROUND
Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART).
METHODS
We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed.
RESULTS
From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01).
CONCLUSIONS
In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).
背景
儿童感染人类免疫缺陷病毒 1 型（HIV-1）后，有效的抗逆转录病毒治疗（ART）选择有限。
方法
我们进行了一项开放性标签、随机、非劣效性试验，比较了基于 HIV 整合酶抑制剂多替拉韦的三药 ART 与标准护理（非多替拉韦为基础的 ART）在开始一线或二线 ART 的儿童和青少年中的疗效。主要终点是通过 Kaplan-Meier 法估计的 96 周时病毒学或临床治疗失败的参与者比例。评估了安全性。
结果
从 2016 年 9 月到 2018 年 6 月，共有 707 名体重至少为 14 公斤的儿童和青少年被随机分配接受多替拉韦为基础的 ART（350 名参与者）或标准护理（357 名）。中位年龄为 12.2 岁（范围，2.9 至 18.0），中位体重为 30.7 公斤（范围，14.0 至 85.0），49%的参与者为女孩。设计上，311 名参与者（44%）开始一线治疗（标准护理组 92%接受依非韦伦为基础的 ART），396 名（56%）开始二线治疗（标准护理组 98%接受强化蛋白酶抑制剂为基础的 ART）。中位随访时间为 142 周。96 周时，多替拉韦组有 47 名参与者和标准护理组有 75 名参与者治疗失败（估计概率分别为 0.14 和 0.22；差异为-0.08；95%置信区间为-0.14 至-0.03；P=0.004）。一线和二线治疗的治疗效果相似（异质性 P=0.16）。多替拉韦组有 35 名参与者和标准护理组有 40 名参与者至少发生了一次严重不良事件（P=0.53），分别有 73 名和 86 名参与者至少发生了一次 3 级或更高级别的不良事件（P=0.24）。多替拉韦组有 5 名参与者和标准护理组有 17 名参与者至少发生了一次 ART 改变不良事件（P=0.01）。
结论
在这项涉及开始一线或二线治疗的 HIV-1 感染儿童和青少年的试验中，多替拉韦为基础的 ART 优于标准护理。（由 ViiV Healthcare 资助；ODYSSEY 临床试验.gov 编号，NCT02259127；EUDRACT 编号，2014-002632-14；和 ISRCTN 编号，ISRCTN91737921。）
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