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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 方啟泰(Chi-Tai Fang) | |
dc.contributor.author | Fan Chi Kit | en |
dc.contributor.author | 范志杰 | zh_TW |
dc.date.accessioned | 2021-07-11T15:09:48Z | - |
dc.date.available | 2021-08-28 | |
dc.date.copyright | 2019-08-28 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-10 | |
dc.identifier.citation | 1.World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing hiv infection recommendations for a public health approach,second edition. 2016.
2.Kanters S, Vitoria M, Doherty M et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. The Lancet HIV 2016; 3: e510-e20. 3.World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: (WHO/CDS/HIV/18.51). Licence: CC BY-NC-SA 3.0 IGO., 2018. 4.World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidance. Geneva: (WHO/CDS/HIV/18.18). Licence: CC BY-NC-SA 3.0 IGO., 2018. 5.World Health Organization. Kanters S, Jansen J, Zoratti M, Forrest J, Humphries B, Campbell J. Web Annex B. Systematic literature review and network meta-analysis assessing first-line antiretroviral treatments In: Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: (WHO/CDS/HIV/18.25). Licence: CC BY-NC-SA 3.0 IGO., 2018. 6.Vineet Prabhu CW, Sarah Jenkins, Saman Nizami, Kelly Catlin, Paul Domanico. New ARVs Could Represent Over USD 3 Billion in Cost Savings Through 2025. Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA, 2016. 7.Vitoria M, Ford N, Clayden P et al. When could new antiretrovirals be recommended for national treatment programmes in low-income and middle-income countries: results of a WHO Think Tank. Curr Opin HIV AIDS 2017; 12: 414-22. 8.Moher D, Liberati A, Tetzlaff J et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097. 9.Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org. 10.Higgins JP, Altman DG, Gotzsche PC et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928. 11.Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available fromguidelinedevelopment.org/handbook. 12.Gatell JM, Assoumou L, Moyle G et al. Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk. AIDS 2017; 31: 2503-14. 13.Trottier B, Lake JE, Logue K et al. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study. Antivir Ther 2017; 22: 295-305. 14.Molina J-M, Ward D, Brar I et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. The Lancet HIV 2018; 5: e357-e65. 15.Blanco JL, Rojas J, Paredes R et al. Dolutegravir-based maintenance monotherapy versus dual therapy with lamivudine: a planned 24 week analysis of the DOLAM randomized clinical trial. J Antimicrob Chemother 2018; 73: 1965-71. 16.Taiwo BO, Marconi VC, Berzins B et al. Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial. Clin Infect Dis 2018; 66: 1794-7. 17.Llibre JM, Hung C-C, Brinson C et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. The Lancet 2018; 391: 839-49. 18.van Lunzen J, Maggiolo F, Arribas JR et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. The Lancet Infectious Diseases 2012; 12: 111-8. 19.Raffi F, Rachlis A, Stellbrink H-J et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. The Lancet 2013; 381: 735-43. 20.Walmsley SL, Antela A, Clumeck N et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 2013; 369: 1807-18. 21.Clotet B, Feinberg J, van Lunzen J et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. The Lancet 2014; 383: 2222-31. 22.Gallant J, Lazzarin A, Mills A et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. The Lancet 2017; 390: 2063-72. 23.Sax PE, Pozniak A, Montes ML et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. The Lancet 2017; 390: 2073-82. 24.Orrell C, Hagins DP, Belonosova E et al. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. The Lancet HIV 2017; 4: e536-e46. 25.Sax PE, DeJesus E, Crofoot G et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. The Lancet HIV 2017; 4: e154-e60. 26.C. Orrell KK, J.A. Coombs, A. Amara, L. Myer, J. Kaboggoza. DolPHIN-1 : Randomised controlled trial of dolutegravir (DTG)- versus efavirenz (EFV)-based therapy in mothers initiating antiretroviral treatment in late pregnancy. 22nd International AIDS Conference, 2018. 27.Dooley KE, Kaplan R, Mwelase N et al. Dolutegravir-Based Antiretroviral Therapy for Patients Co-Infected with Tuberculosis and Hiv: A Multicenter, Noncomparative, Open-Label, Randomized Trial. Clin Infect Dis 2019. 28.A Cournil CK, S Eymard-Duvernay, S Lem, M Mpoudi-Ngole, P Omgba. Dolutegravir- versus an efavirenz 400 mg-based regimen for the initial treatment of HIV-infected patients in Camer- oon: 48-week efficacy results of the NAMSAL ANRS 12313 trial. J Int AIDS Soc, 2018. 29.Cahn P, Pozniak AL, Mingrone H et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. The Lancet 2013; 382: 700-8. 30.Aboud M, Kaplan R, Lombaard J et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. The Lancet Infectious Diseases 2019; 19: 253-64. 31.McComsey GA, Lupo S, Parks D et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS 2018; 32: 477-85. 32.Rutherford GW, Horvath H. Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Efavirenz Plus Two Nucleoside Reverse Transcriptase Inhibitors As Initial Antiretroviral Therapy for People with HIV: A Systematic Review. PLoS One 2016; 11: e0162775. 33.Jiang J, Xu X, Guo W et al. Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials. AIDS Res Ther 2016; 13: 30. 34.Llibre JM, Montoliu A, Miro JM et al. Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort. HIV Med 2019; 20: 237-47. 35.World Health Organization. Guidelines on the public health response to pretreatment HIV drug resistance,Geneva Licence: CC BY-NC-SA 3.0 IGO. 2017. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78650 | - |
dc.description.abstract | 研究目的
自2018年,世界衛生組織(World Health Organization, WHO)建議使用Dolutegravir(DTG)配合兩種核苷酸反轉錄酶抑制劑(nucleoside reverse transcriptase inhibitors, NRTIs)為抗反轉錄病毒療法(antiretroviral therapy, ART),作為成人和青少年治療初期感染人類免疫缺乏病毒(human immunodeficiency virus, HIV)的首選用藥,指引基於WHO其自行發起的系統性文獻回顧及網絡統合分析研究,發現DTG為本的處方(DTG-based)相較於其他ART處方,特別是以往被建議一線使用的Efavirenz為本的處方(EFV-based),能表現更有效的病毒抑制成功率、CD4細胞數恢復率及較低的用藥中止治療風險。但即便如此,分析使用了有限數量直接比較(head-to-head)的隨機對照試驗(randomized control trials, RCTs),而目前已有更多已完成且設計良好的RCTs發表,所以我們希望可以整理出更有系統且最完整的證據,回答DTG-based處方其療效和耐受性兩大面向,進行一個更全面的統合分析。 方法 自Pudmed,Embase,Cochrane database,AIDSinfo和Clinicaltrial.gov等資料庫進行文獻搜尋,搜尋結果到2019年5月,納入相關的RCTs做為分析,篩選符合的文獻會進行偏差風險(Risk of bias)評估。療效結果以FDA演算法(snapshot algorithm)為定義;耐受性結果以任何藥物產生的副作用(Adverse events, AEs)所導致研究過程中停止用藥為定義,結果都以風險比(risk ratio, RRs)作基準。當中也使用次群組分析(subgroup analysis)和敏感度分析(sensitivity analysis),獨立分析不同病理狀況的HIV感染者,比較DTG與其他ART之間的特徵差異。 結果 共納入了19篇RCTs,總包括8936名HIV感染者,當中分成三種HIV感染者狀態:(1)已達到病毒學抑制(virally suppressed)、(2)從未接受過任何ART治療(treatment-naive)和(3)接受過ART治療但治療失敗(treatment-experienced)。6篇RCTs評估了已達到病毒學抑制的HIV感染者; 在比較DTG-based和其他ART治療之間,病毒抑制(RR 0.95, 95 % CI 0.42-2.16)和因副作用產生而停藥發生率(RR 2.65, 95%CI 0.59-11.93)都無統計上顯著的差異,但估計的效果顯示該群組的感染者在轉換成DTG為本的處方後,因副作用產生而停藥發生率的比例有明顯較高的風險。11篇RCTs評估了從未接受過任何ART治療的HIV感染者; 在使用DTG-based的情況下,比較使用EFV-based和蛋白酶抑製劑為本(protease inhibitor, PI-based)的次群組分析,顯示出病毒抑制和停藥發生率都有正向的效果。2篇RCTs評估了接受過ART首選治療但失敗的感染者,結果顯示以DTG-based的治療,其病毒抑制(RR 1.16, 95%CI 1.08-1.24)和因副作用產生而停藥發生率(RR 0.56, 95%CI 0.31-1.00)風險都較其他ART處方,呈現正向的效果。 結論 我們統合分析結果建議以DTG為本的抗反轉錄病毒處方可作為HIV感染者,治療人類免疫缺乏病毒一線首選和首選用藥失敗後二線替代時的用藥選擇。但考慮使用於已達到病毒學抑制的HIV感染者並選擇轉換使用DTG處方時,應採取謹慎且長期追蹤的措施。 | zh_TW |
dc.description.abstract | Background
Since 2018, World Health Organization (WHO) recommended Dolutegravir (DTG) plus two nucleoside reverse-transcriptase inhibitors (NRTIs) antiretroviral therapy (ART) as the preferred first-line regimen for treatment-naive HIV-positive adults and adolescents as because which showed DTG-based regimen was more effective with higher viral suppression rate, better CD4 cell count recovery and lower risk of treatment discontinuation compared with another widely used first-line regimen, Efavirenz (EFV)-based ART, after WHO self-initiated systematic review and network meta-analysis. Since the synthesized results of previous meta-analysis with a limited number of head-to-head randomized control trials (RCTs), and to date there were several newly published and robust RCTs available, we aimed to conducted a comprehensive meta-analysis of efficacy and tolerability outcome of DTG-based regimens. Methods Pudmed, Embase, Cochrane databases, AIDSinfo and Clinicaltrial.gov were searched up to May 2019 for RCTs on DTG-based regimen in HIV-positive patients. Efficacy was analysed by FDA snapshot algorithm, and tolerability was defined as any adverse events leading to study drug discontinuation. Each various characteristics of HIV participants were considered in subgroup and sensitivity analysis. Risk of bias and certainty of evidences were also assessed. Results Nineteen eligible RCTs comprising 8936 patients were included, which were divided into three scenarios: virally suppressed, treatment-naive and treatment-experienced. Among 6 trials assessing virally suppressed populations, no significant difference was shown in terms of viral suppression (RR 0.95, 95 % CI 0.42 to 2.16) and discontinuation rate (RR 2.65, 95 % CI 0.59 to 11.93) between DTG-based and others ART regimens, but the estimated effect showed higher proportions of discontinuation rate of study drug related to adverse events after switch to DTG-based regimen. Among 11 trials assessing treatment-naive populations, beneficial effects of viral suppression and discontinuation rate were showed for DTG-based regimen compared with EFV-based and protease inhibitor (PI-) based regimens after a subgroup analysis. Only 2 trials assessed treatment-experienced populations, which showed a significant difference of better viral suppression (RR 1.16, 95 % CI 1.08 to 1.24), and lower discontinuation rates (RR 0.56, 95 % CI 0.31 to 1.00) for DTG-based regimen. Conclusion Our meta-analysis showed that DTG-based regimen was a preferred ART regimen for first-line and second-line regimen among HIV-positive patients, but for virally suppressed patients, cautions should be taken and long-term follow-up is needed. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T15:09:48Z (GMT). No. of bitstreams: 1 ntu-108-R06847029-1.pdf: 2513327 bytes, checksum: 5dc014825f694fc0a9673da03d1f3418 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員會審定書 ii
摘要 iii Abstract v Tables of Contents viii List of Tables ix List of Figures x 實習單位簡介 xi Chapter 1: Introduction 1 Chapter 2: Methods 3 2.1 Inclusion and exclusion criteria 3 2.2 Search strategy and selection criteria 4 2.3 Data extraction 4 2.4 Assessment of quality of included studies 5 2.5 Data synthesis and statistical analysis 5 2.6 Sensitivity analysis 6 2.7 Assessment of certainty of evidence 6 Chapter 3: Result 8 3.1 Efficacy 9 3.2 Tolerability 12 3.3 Quality assessment 14 Chapter 4: Discussion 16 Reference 21 Table 1 PubMed and Embase search strategy 25 Table 2 Characteristics of patients included in the selected randomized control trial studies 26 Table 3 Summary of findings: certainty of evidence for HIV virally suppressed patients 28 Table 4 Summary of findings: certainty of evidence for HIV treatment-naive patients: DTG-based versus Efavirenz-based 29 Table 5 Summary of findings: certainty of evidence for HIV treatment-naive patients: DTG-based versus Protease inhibitors-based 30 Table 6 Summary of findings: certainty of evidence for HIV treatment-naive patients: DTG-based versus others generations of InSTI-based 31 Table 7 Summary of findings: certainty of evidence for HIV treatment-experienced patients 32 Figure 1 Flow chart of articles identified, screened, assessed and included 33 Figure 2a Assessment of the risk of bias by Cochrane Collaboration tool: risk of bias summary 34 Figure 2b Assessment of the risk of bias by Cochrane Collaboration tool: risk of bias graph 35 Figure 3a Virally suppressed patients reached virological non-response 36 Figure 3b Virally suppressed patients reached virological non-response, stratified by follow-up duration endpoint 37 Figure 4a Treatment-naive patients achieved viral suppression 38 Figure 4b Treatment-naive patients achieved viral suppression with sensitivity analysis, excluding DoIPHIN-1 and INSPIRING 39 Figure 5 Treatment-naive patients with subgroup analysis of viral suppression among regimens of different mechanisms of action 40 Figure 6 Treatment-experienced patients who failed the first-line regimens, and achieved viral suppression 41 Figure 7 Tolerability, defined as any adverse events leading to discontinuation of study drug in three sub-population patients 42 Figure 8 Treatment-naive patients with subgroup analysis of tolerability among regimens of different mechanisms of action 43 | |
dc.language.iso | en | |
dc.title | 以Dolutegravir為本的抗反轉錄病毒處方相較於其他處方之療效及耐受性:統合分析 | zh_TW |
dc.title | Efficacy and Tolerability of Dolutegravir (DTG) Based Antiretroviral Therapy Compared to Other Combination Antiretroviral Therapy for HIV-Positive Patients: A Meta-Analysis | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林淑文(Shu-Wen Lin),洪健清(Chien-Ching Hung) | |
dc.subject.keyword | 人類免疫缺乏病毒,抗反轉錄病毒藥物,整合?抑制劑,療效,耐受性, | zh_TW |
dc.subject.keyword | human immunodeficiency virus (HIV),antiretroviral therapy (ART),dolutegravir (DTG),efficacy,tolerability, | en |
dc.relation.page | 43 | |
dc.identifier.doi | 10.6342/NTU201902988 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-12 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 公共衛生碩士學位學程 | zh_TW |
顯示於系所單位: | 公共衛生碩士學位學程 |
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