目的本研究旨在系统评价基于既往冠状病毒肺炎的研究,进而探索洛匹那韦/利托那韦(LPV/r)用于2019新型冠状病毒肺炎的临床可行性。方法在计算机检索中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库(Wangfang Da...目的本研究旨在系统评价基于既往冠状病毒肺炎的研究,进而探索洛匹那韦/利托那韦(LPV/r)用于2019新型冠状病毒肺炎的临床可行性。方法在计算机检索中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库(Wangfang Data)、中国生物医学文献数据库(CBM)、PubMed、Web of Science、EMBASE等数据库检索相关研究。此外,检索中文医药类报刊、WHO以及美国和中国CDC网站、已发表文献的相关参考文献等作为辅助。检索时间范围为2003年1月到2020年1月24日。研究纳入标准:研究纳入标准:(1)研究为比较洛匹那韦/利托那韦与安慰剂/标准治疗方案用于严重急性呼吸综合征(SARS)、中东综合征(MERS)患者;(2)临床结局进行评价临床队列研究和病例-对照研究;(3)诊断根据WHO公布的确诊或疑似SARS或MERS病例的诊断标准,但不排除流行初期诊断为感染的病例;(4)对同一研究多次发表的报告,我们从提供最详细信息的报告中提取资料;(5)指南性文件,包括:临床指南、国家级学会/团体的专家共识。排除标准:(1)仅有摘要无全文的文献资料以及数据不完整无法利用的文献;(2)离体细胞试验。两名评价员独立提取研究设计、对象及诊断标准、干预方案、结局(包括死亡、并发症、症状、生活质量、激素的使用、胸部影像及药物不良反应)等资料进行统计分析。结果通过文献检索,发现潜在相关文章230篇,初筛后获得44篇文章,最终纳入4个研究。结果提示LPV/r的药物方案的早期应用能够降低SARA患者病死率,减少糖皮质激素用量,对控制患者治疗后期并发症具有重要意义。结论LPV/r可以作为一种试验性疗法用于2019-nCoV肺炎(尤其是新发感染者)的抗病毒治疗,并应该为此尽快开展真实世界临床研究,进一步探索LPV/r早期用于2019-nCoV新型肺炎的临床效应。展开更多
Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-riton...Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.展开更多
文摘目的本研究旨在系统评价基于既往冠状病毒肺炎的研究,进而探索洛匹那韦/利托那韦(LPV/r)用于2019新型冠状病毒肺炎的临床可行性。方法在计算机检索中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库(Wangfang Data)、中国生物医学文献数据库(CBM)、PubMed、Web of Science、EMBASE等数据库检索相关研究。此外,检索中文医药类报刊、WHO以及美国和中国CDC网站、已发表文献的相关参考文献等作为辅助。检索时间范围为2003年1月到2020年1月24日。研究纳入标准:研究纳入标准:(1)研究为比较洛匹那韦/利托那韦与安慰剂/标准治疗方案用于严重急性呼吸综合征(SARS)、中东综合征(MERS)患者;(2)临床结局进行评价临床队列研究和病例-对照研究;(3)诊断根据WHO公布的确诊或疑似SARS或MERS病例的诊断标准,但不排除流行初期诊断为感染的病例;(4)对同一研究多次发表的报告,我们从提供最详细信息的报告中提取资料;(5)指南性文件,包括:临床指南、国家级学会/团体的专家共识。排除标准:(1)仅有摘要无全文的文献资料以及数据不完整无法利用的文献;(2)离体细胞试验。两名评价员独立提取研究设计、对象及诊断标准、干预方案、结局(包括死亡、并发症、症状、生活质量、激素的使用、胸部影像及药物不良反应)等资料进行统计分析。结果通过文献检索,发现潜在相关文章230篇,初筛后获得44篇文章,最终纳入4个研究。结果提示LPV/r的药物方案的早期应用能够降低SARA患者病死率,减少糖皮质激素用量,对控制患者治疗后期并发症具有重要意义。结论LPV/r可以作为一种试验性疗法用于2019-nCoV肺炎(尤其是新发感染者)的抗病毒治疗,并应该为此尽快开展真实世界临床研究,进一步探索LPV/r早期用于2019-nCoV新型肺炎的临床效应。
基金Frontier Biotechnologies Inc.,Ministry of Science and Technology of China(Nos.2013ZX09101001 and 2017ZX09201007)the Beijing Municipal of Science and Technology Major Project(Nos.D141100000314005,D141100000314002,and D161100000416003)+1 种基金the National Natural Science Foundation of China(Nos.81772165,81974303,and 81571973)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.
