多替拉韦单药治疗与多替拉韦/阿巴卡韦/拉米夫定治疗慢性人类免疫缺陷病毒感染病毒学抑制患者的比较：TiviCAY试验的随机非劣效单药治疗
Dolutegravir Monotherapy Versus Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed People Living With Chronic Human Immunodeficiency Virus Infection: The Randomized Noninferiority MONotherapy of TiviCAY Trial.
作者信息
Hocqueloux Laurent, Raffi François, Prazuck Thierry, Bernard Louis, Sunder Simon, Esnault Jean-Luc, Rey David, Le Moal Gwenaël, Roncato-Saberan Mariam, André Marie, Billaud Eric, Valéry Antoine, Avettand-Fènoël Véronique, Parienti Jean-Jacques, Allavena Clotilde
机构信息
Service des Maladies Infectieuses et Tropicales, CHR d'Orléans-La Source, Tours.
Service des Maladies Infectieuses, CHU Hôtel Dieu and INSERM UIC 1413 Nantes University, Tours.
出版信息
Clin Infect Dis. 2019 Oct 15;69(9):1498-1505. doi: 10.1093/cid/ciy1132.
BACKGROUND
We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful dolutegravir-based triple therapy.
METHODS
MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/μL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart.
RESULTS
Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval [CI], -5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy.
CONCLUSIONS
Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection.
CLINICAL TRIALS REGISTRATION
NCT02596334 and EudraCT 2015-002853-36.
背景
我们调查了度鲁特韦（DTG）单药治疗是否可用于维持接受基于度鲁特韦的成功三联疗法的人类免疫缺陷病毒（HIV）感染者的病毒学抑制。
方法
MONCAY（TiviCAY单药治疗）是一项为期48周的多中心、随机、开放标签、非劣效性 margin 为12%的试验。CD4最低点>100/μL、血浆HIV-1 RNA<50拷贝/mL持续≥12个月且接受DTG/阿巴卡韦（ABC）/拉米夫定（3TC）稳定方案治疗的患者按1:1随机分组，继续原方案或改为DTG单药治疗。主要终点是意向性治疗快照分析中第24周时HIV RNA<50拷贝/mL的患者比例。病毒学失败（VF）定义为在2周内连续两次HIV RNA>50拷贝/mL。
结果
78例患者被分配至DTG单药治疗组，80例继续接受DTG/ABC/3TC治疗。至第24周时，DTG组有2例患者出现VF且对整合酶链转移抑制剂（INSTI）类药物无耐药；1例患者因不良事件停用DTG/ABC/3TC。DTG治疗组第24周的成功率为73/78（93.6%），DTG/ABC/3TC治疗组为77/80（96.3%）（差异为2.7%；95%置信区间[CI]，-5.0至10.8）。在随后的随访中，DTG组又发生了5例VF（其中2例出现对INSTI的新出现耐药突变）。DTG治疗组第48周时VF的累积发生率为9.7%（95%CI，2.8至16.6），而DTG/ABC/3TC治疗组为0%（对数秩检验P = 0.005）。数据安全监测委员会建议用标准化三联疗法加强DTG治疗组。
结论
由于VF伴耐药的风险随时间增加，我们建议在慢性HIV感染者中避免将DTG单药治疗作为维持策略。
临床试验注册
NCT02596334和EudraCT 2015-002853-36。
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