Objective To explore the efficacy of a combination regimen by Lopinave/Litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for the treatment of novel coronavirus pneumonia (NCP).Methods We design the protocol as a real world study, which includes two groups: prospective intervention cohort (T1) and historical control group (T2). For T1 group, ninety patients will be enrolled who are diagnosed as NCP. All patients in T1 group will receive standard therapies following the recommendation in the guidelines of National Commission of Health, and they will be administered an anti-virus regimen includes LPV/r and FTC/TAF. The T2 group will enroll patients who have received single regimen includes LPV/r. The major outcome is the survival rate of patients. Secondary outcomes are the time of seroconversion of RNA, ARDS progression rate and length of hospital stay.Conclusions The results of this real world study might provide clinical practitioners a high efficiency and fast antivirus regimen for NCP. In addition, the conduction of this study will accelerate screening for other new effective therapeutic method.

Objective:To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.Methods:Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses).Results:Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing.Conclusions:ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

目的 本研究旨在系统评价以富马酸替诺福韦二吡呋酯(tenofovir disoproxil fumarate,TDF)为基石(backbone)的抗反转录病毒方案(antiretroviral therapy,ART),与以替诺福韦艾拉酚胺(tenofovir alafenamide,TAF)为基石的ART方案对于非初治(experienced treatment)HIV感染者的长期有效性和安全性的影响.方法 在PubMed,EMBASE,Web of Science,Cochrane Library和中国生物医学文献数据库检索相关临床随机对照试验(randomized controlled trial,RCT),时间范围为2003-2019年.患者纳入标准:①HIV-1感染者,接受过抗病毒治疗(experienced treatment);②入组时的病毒载量(viral load,VL)<50 copies/ml;③eGFR>50 ml/min;④≥12岁的儿童及成年人;5)随访时间≥96周,排除标准:①HIV-1初诊患者(naive);②VL≥50 copies/ml;③<12岁的儿童;④妊娠;⑤合并丙肝/乙肝.有效性评价指标采用病毒抑制成功率,同时采用符合方案分析(Per-protocol Analysis,PP分析)和意向性分析(Intention-to-treat Analysis,ITT分析),若两者结果不一致,以ITT分析结果作为最终结论.安全性评价指标包括:骨密度变化、肾脏功能变化及药物相关的退出率.采用Rev Man 5.3进行Meta分析.结果 通过文献检索,发现潜在相关文章84篇,初筛后获得62篇文章,最终纳入3个研究,包含2729例患者.PP分析中,TAF方案与TDF方案对患者的病毒抑制成功率相似(RR=0.99,95％CI:0.98～1.00,P=0.25),ITT分析的结果与PP分析一致.三项研究均报告了患者的骨密度指标,但均采用骨密度均数变化曲线方式报告,无法进行数据合并,对3个研究进行定性系统评价,TAF治疗后患者的骨密度均显著增加,TDF则显著降低.三项研究均报告了患者肾功能指标(urine protein to creatinine ratio,UACR)变化情况,但数值报告的方式不一致,无法进行数据合并,行定性评价,结果显示TAF治疗后患者的肾功能显著好于TDF方案.TAF组患者退出率较TDF组有降低趋势,但差异不显著(RR=0.75,95％CI:0.52～1.11,P=0.15),对药物相关退出率做亚组分析,两组方案结果相似(RR=2.71,95％CI:0.30～24.45,P=0.38).结论 以TAF为基石和以TDF为基石的ART方案用于非初治HIV感染者长期治疗的有效性相似.在肾功能、骨密度以及耐受性等方面,TAF方案均优于TDF方案,显示出其长期安全性的优势,但限于样本量和观察时间,上述结论尚待更多高质量RCT进一步验证.