替诺福韦艾拉酚胺与富马酸替诺福韦二吡呋酯对非初治艾滋病患者长期安全性和有效性影响的Meta分析和系统评价  

The Long-term Safety and Efficacy of Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate for Experienced Treatment HIV Patients:A Meta-analysis and Systematic Review

作　　者：邓洪飞 曾俊[1,2,3] 王宇 刘辉[1] 江华 DENG Hongfei;ZENG Jun;WANG Yu;LIU Hui;JIANG Hua(Institute for Emergency and Disaster Medicine,Sichuan Provincial People’s Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,Sichuan Province,China;School of Medicine,University of Electronic Science and Technology of China,Chengdu 610054,Sichuan Province,China;Emergency Center,Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital,Chengdu 610072,Sichuan Province,China)

机构地区：[1]电子科技大学附属医院.四川省人民医院急诊医学与灾难医学研究所,成都610072 [2]电子科技大学医学院,成都610054 [3]四川省医学科学院·四川省人民医院急救中心,成都610072

出　　处：《预防医学情报杂志》2019年第12期1329-1340,共12页Journal of Preventive Medicine Information

基　　金：国家市场监督总局委托项目(项目编号：2019006);四川省科技支撑计划项目(项目编号：2014FZ0125)

摘　　要：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2 729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=0.75,95Objective To systematically evaluate the effect of tenofovir disoproxil fumarate as backbone of ART and tenofovir alafenamide as backbone of ART on the long-term effectiveness and safety of experienced treatment HIV infection. Methods Articles published in PubMed, EMBASE,Web of Science, Cochrane Library, CBD(Chinese biomedical literature database) database from2003 to 2019 were searched. The inclusion criteria for patients were HIV-infected, experienced treatment(HIV-1 RNA <50 copies/mL) children and adults aged 12 or older with estimated glomerular filtration(eGFR) rate >50 mL/min for at least 60 weeks. Participants who are na?ve HIV infection or living with HIV-1 RNA ≥50 copies/mL or children under 12 years old or pregnancy or combined with hepatitis B/C were excluded. The efficacy evaluation index is the virus suppression rate. Meanwhile,per-protocol analysis and intention-to-treat analysis are adopted. If the two results are inconsistent,the latter result will be taken as the final conclusion. Changes in bone mineral density, renal function and drug-related dropout rates are used as safety indicators. Rev Man 5.3 was used for Meta-analysis. Result A total of 84 potential related articles were searched,and 62 articles were obtained after preliminary screening. Finally,3 studies were used for analysis,including 2 729 patients. In per-protocol analysis, the virus suppression rate in patients with TAF and TDF was similar(RR=0.99,95%CI:0.98-1.00,P=0.25). Intention-to-treat analysis also showed the same results. The BMD indicators of patients were reported in all three studies;however, the BMD mean change curve was used, and the data could not be integrated. Qualitative and systematic evaluation was conducted on the three studies. BMD of patients after TAF treatment was significantly increased, while TDF was significantly decreased. Changes in urine protein to creatinine ratio(UACR) were reported in all three studies;however, data combination and qualitative evaluation was impossible due to the differences of the

关 键 词：富马酸替诺福韦二吡呋酯 替诺福韦艾拉酚胺 HIV META分析 

分 类 号：R512.91[医药卫生—内科学]