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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 洪健清(Chien-Ching Hung) | |
dc.contributor.author | I-Wen Chen | en |
dc.contributor.author | 陳怡文 | zh_TW |
dc.date.accessioned | 2023-03-19T22:58:34Z | - |
dc.date.copyright | 2022-10-03 | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022-07-26 | |
dc.identifier.citation | [1] Vitoria M, Rangaraj A, Ford N, Doherty M. Current and future priorities for the development of optimal HIV drugs. Curr Opin HIV AIDS 2019; 14(2):143-149. [2] Crawford KW, Ripin DHB, Levin AD, Campbell JR, Flexner C. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement. Lancet Infect Dis 2012; 12:550–560. [3] Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV, 2019. Available at: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf [4] European AIDS clinical society. EACS Guidelines 10.1, 2020. Available at: https://www.eacsociety.org/files/guidelines-10.1_5.pdf [5] U.S. department of health and human services food and drug administration center for drug evaluation and research. Human immunodeficiency virus-1 Infection: developing antiretroviral drugs for treatment-guidance for industry, 2015. Available at: https://www.fda.gov/media/86284/download [6] Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analysis. BMJ 2003; 327(7414):557-560. [7] Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The cochrane collaboration’s tool for accessing risk of bias in randomised trial. BMJ 2011; 343:d5928. [8] Sax PE, Dejesus E, Crofoot G, Ward D, Benson P, Dretler R, 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. Lancet HIV 2017; 4(4):e154-e160. [9] Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, 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. Lancet 2017; 390(10107):2063-2072. [10] Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, 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. Lancet 2017; 390(10107):2073-2082. [11] Molina JM, Ward D, Brar I, Mills A, Stellbrink HJ, Lopez-Cortes L, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adult with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV 2018; 5(7):e357-365. [12] Daar ES, Dejesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3 non-inferiority trial. Lancet HIV 2018; 5(7):e347-356. [13] Kityo C, Hagins D, Koenig E, Avihingsanon A, Chetchotisakd P, Supparatpinyo K, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed HIV-1 infected women: a randomized, open-label, multicenter, active-controlled, phase 3, noninferiority trial. J Acquir Immune Defic Syndr 2019; 82(3): 321-328. [14] Sax PE, Rockstroh JK, Luetkemeyer AF, Yazdanpanah Y, Ward D, Trottier B, et al. Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV. Clis Infect Dis 2020. ciaa988. doi: 10.1093/cid/ciaa988. [15] Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, et al. Patient-reported symptoms over 48 weeks among participants in randomized, double-blind, phase III non-inferiority trial of adults with HIV on co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus co-formulated abacavir, dolutegravir, and lamivudine. Patient 2018; 11(5):561-573. [16] Tsiang M, Jones GS, Goldsmith J, Mulato A, Hansen D, Kan E, et al. Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profile. Antimicrob Agents Chemother 2016; 60(12):7086–97. [17] Young J, Xiao Y, Moodie EEM, Abrahamowicz M, Klein MB, Bernasconi E, Schmid P, et al. Effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study. J Acquir Immune Defic Syndr 2015; 69(4):413-421. [18] Marcus JL, Neugebauer RS, Leyden WA, Chao CR, Xu L, Quesenberry Jr CP, et al. Use of abacavir and risk of cardiovascular disease among HIV-infected individuals. J Acquir Immune Defic Syndr 2016; 71(4):413-419. [19] De Ven NSV, Pozniak AL, Levi JA, Clayden P, Garratt A, Redd C, et al. Analysis of pharmacovigilance database for dolutegravir safety in pregnancy. Clin Infect Dis 2020; 70(12):2599-2606. [20] Castagna A, Maggiolo F, Penco G, Wright D, Mills A, Grossberg R, et al. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir- resistant HIV-1: 24-Week results of the phase III VIKING-3 study. J Infect Dis 2014; 210(3):354-62. [21] Biktarvy [package insert]. Foster City, CA: Gilead Sciences; 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85337 | - |
dc.description.abstract | 主要目標: 收集已發表之臨床試驗結果,進行HIV感染者使用固定劑量併用製劑Bictegravir/Emtricitabine/Tenofovir Alafenamide的療效與安全性的統合分析。 研究方法: 符合納入條件的隨機分配臨床試驗資料將進行統合分析比較使用固定劑量併用製劑BIC/FTC/TAF與已上市核准的抗病毒藥物包含非核苷酸反轉錄酶抑制劑、蛋白酶抑制劑、或嵌入酶抑制劑加上兩種核苷酸反轉錄酶抑制劑的療效與安全性。使用Mantel-Haenszel model分析兩組之間的異質性。I2會用來評估應使用fixe-effect model或是random-effect model進行統合分析。 結果: 本統合分析共納入7個隨機分組的臨床研究。包含3540名受試者 (其中3個臨床試驗研究收納沒有接受過任何抗反轉錄藥物治療的受試者而另外4個臨床試驗研究則收納已接受抗反轉錄藥物穩定治療的受試者)。在第48週療效分析發現BIC/FTC/TAF組與對照組並無統計顯著(odds ratio [OR], 1.07 [95% CI, 0.83, 1.38])。同時,BIC/FTC/TAF的安全性與對照組也沒有統計顯著: 所有發生的不良事件 OR 0.93 (95% CI, 0.79, 1.09]、Grade 3 或 Grade 4發生的不良事件OR 0.93 [95% CI, 0.79, 1.09]、與藥物相關的不良事件 OR 1.32 [95% CI, 0.68, 2.54]。 結論: BIC/FTC/TAF組與其他有效藥對照組在第48週時都有相當高的病毒抑制效果。雖然每個臨床試驗的設計都不一樣而導致部分分析的異質性較高,但固定劑量併用製劑BIC/FTC/TAF仍可以給予HIV感染者一個簡單、有效且安全的治療選擇。 | zh_TW |
dc.description.abstract | Objective: This meta-analysis aimed to systematically review the efficacy and safety of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people living with HIV (PLWH). Methods: Randomized controlled trials (RCT) were included to compare the efficacy and safety between BIC/FTC/TAF and other antiretroviral regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase strand transfer inhibitor plus two nucleoside reverse-transcriptase inhibitors. Mantel-Haenszel model was used to investigate the combination or interaction of a group of independent studies. I2 was used to determine whether a fixed-effect model or random-effect model was to be used. Results: A total of seven studies including 3540 participants were analyzed (three studies conducted in antiretroviral-nave PLWH and four in stably antiretroviral-treated PLWH). At week 48, the efficacy with BIC/FTC/TAF was not statistically significantly different from that with control regimens (odds ratio [OR], 1.07 [95% CI, 0.83, 1.38]). BIC/FTC/TAF had comparable safety profiles to control regimens: OR for all adverse effects (AEs) was 0.93 (95% CI, 0.79, 1.09]; OR for any grade 3 or grade 4 AEs was 0.97 (95% CI, 0.66, 1.41]; and OR for treatment-related AEs was 1.32 (95% CI, 0.68, 2.54). Conclusions: Both BIC/FTC/TAF and the active control regimens led to similarly high levels of viral suppression among antiretroviral-nave and antiretroviral-treated PLWH at week 48. The inter-study differences in selected populations and control regimens may lead to the high heterogeneity for the meta-analysis. The fixed-dose combination tablet of BIC/FTC/TAF can provide antiretroviral-nave or stably antiretroviral-treated PLWH with a simple, efficacious and well-tolerated treatment option. | en |
dc.description.provenance | Made available in DSpace on 2023-03-19T22:58:34Z (GMT). No. of bitstreams: 1 U0001-1207202223210100.pdf: 2793324 bytes, checksum: 7a03821afc8502949df72474ae250841 (MD5) Previous issue date: 2022 | en |
dc.description.tableofcontents | 誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS v 1. Introduction 1 2. Methods 3 2.1 Search Strategy 3 2.2 Eligibility Criteria 3 2.3 Outcomes 4 2.4 Data Extraction 4 2.5 Statistical Analysis 4 3. Results 6 3.1 Overview of literature search 6 3.2 Study Characteristics 6 3.3 Efficacy profile of BIC/FTC/TAF versus other control groups at Week 48 7 3.4 Change of CD4 cell count at Week 48 8 3.5 Safety profile of BIC/FTC/TAF versus other control groups 9 3.6 Weight Changes of BIC/FTC/TAF versus control group from baseline 9 4. Discussion 11 5. Conclusions 17 6. Acknowledgement 18 6.1 Statement of ethics compliance 18 6.2 Data Availability 18 6.3 Funding 18 6.4 Authors’ Contributions 18 6.5 Authorship 18 6.6 Transparency Declaration 18 6.7 Disclosures 18 7. References 20 8. Tables 24 Table 1. Selected eligible studies after systematic review. 24 Table 2. Basic characteristics of the selected studies. 26 9. Figures 28 Figure 1. PRISMA flow chart of the selection process for identification of eligible studies for pooling. 28 Figure 2. Meta-analysis shown in forest plot for the efficacy with BIC/FTC/TAF versus other control groups. 29 Figure 3. Forest plot for the treatment difference 29 Figure 4. Funnel plot for the selected studies is symmetrical, which indicates low risk of publication bias. 30 Figure 5. Forest plot for changes in CD4 cell count from baseline to Week 48 30 Figure 6. Forest plot for adverse events from baseline to week 48 31 Figure 7. Forest plot for weight change from baseline to week 48 for 4030 study and week 144 for 1489 and 1490 studies 32 Clinical Protocol page 1 TABLE OF CONTENTS page 2 GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS page 5 1 Introduction page 8 1.1 Background page 8 1.2 BIC/FTC/TAF page 9 1.3 Rationale for this study page 11 1.4 Compliance page 13 2 Objectives page 14 3 Study Design page 15 3.1 Endpoints page 15 3.2 Study Design page 15 3.3 Study Treatments page 17 3.4 Duration of Study page 17 3.5 Number of Planned Participants page 18 3.6 Method of Assigning Patients to Treatment Groups page 18 3.7 Removal from Therapy or Assessment page 18 3.7.1 Discontinuation of Study Drug or Declining Procedural Assessment page 18 3.7.2 Stopping a Participant’s Study Participation page 19 4 Selection and Withdrawal of Patients page 22 4.1 Inclusion Criteria page 22 4.2 Exclusion Criteria page 24 5 Investigational Medicinal Products page 26 5.1 Randomization page 26 5.2 Description and Handling page 26 5.2.1 Formulation page 26 5.2.2 Mechanism of Action page 27 5.2.3 Packaging page 28 5.2.4 Storage page 28 5.3 Dosage and Administration of BIC/FTC/TAF page 29 5.4 Prior and Concomitant Medications page 29 6 Study Procedures page 31 6.1 Participant Enrollment and Treatment Assignment page 31 6.2 Pre-treatment Assessments page 31 6.2.1 Screening Visit page 31 6.2.2 Run-in Visit page 32 6.3 Randomization page 33 6.4 Treatment Assessment page 33 6.4.1 Day 1/Baseline Assessment (Treatment Period) page 33 6.4.2 Week 4 to Week 48 (Treatment Period) page 34 6.5 Post-treatment Assessment page 36 6.5.1 Early Study Drug Discontinuation (ESDD) Visit page 36 6.5.2 30-Day Follow-Up Visit page 37 6.6 Post Study Care page 38 6.7 Virologic Failure page 38 6.7.1 Management of Virologic Rebound page 38 6.7.2 Participants with HIV-1 RNA ≥ 50 copies/mL at ESDD or Week 48 page 40 7 Adverse Events and Toxicity Management page 41 7.1 Definitions of Adverse Events and Serious Adverse Events page 41 7.1.1 Adverse Events page 41 7.1.2 Serious Adverse Events page 41 7.2 Assessment of Adverse Events and Serious Adverse Events page 42 7.2.1 Assessment of Causality for Study Drugs and Procedures page 42 7.2.2 Assessment of Severity page 42 7.3 Investigator Requirement and Instruction for Reporting Adverse Event and Serious Adverse Event page 43 7.3.1 Adverse Events page 43 7.3.2 Serious Adverse Events page 43 7.4 Toxicity Management page 43 7.4.1 Grade 1 and Grade 2 Laboratory Abnormality or Clinical Event page 44 7.4.2 Grade 3 Laboratory Abnormality or Clinical Event page 44 7.4.3 Grade 4 Laboratory Abnormality or Clinical Event page 44 8 Statistical Considerations page 45 8.1 Analysis Objectives and Endpoints page 45 8.1.1 Analysis Objectives page 45 8.1.2 Primary Endpoints page 45 8.1.3 Secondary Endpoints page 45 8.2 Analysis Conventions page 46 8.2.1 Analysis Sets page 46 8.3 Data Handling Conventions page 47 8.4 Demographic Data and Baseline Characteristics page 48 8.5. Efficacy Analysis page 48 8.5.1 Primary Analysis page 48 8.5.2 Secondary Analysis page 50 8.6. Safety Analysis page 50 8.6.1 Secondary Analysis page 51 8.6.2 Adverse Events page 51 8.6.3 Laboratory Evaluations page 51 8.6.4 Other Safety Evaluations page 52 8.7. Pharmacokinetic Analysis page 52 8.8. Patient-Reported Outcome page 52 8.9. Sample Size page 52 8.10. Analysis Schedule page 53 9 Responsibilities page 54 9.1. Ethical and Regulatory Considerations page 54 9.2. Informed Consent page 54 9.3. Data Protection page 56 9.4. Data Quality Assurance page 56 9.5. Source Documents page 57 9.6. Study Start and Closure page 58 9.7. Protocol Compliance page 59 10 References page 60 Appendix 1. Pregnancy Precautions, Definition for Female of Childbearing Potential, and Contraceptive Requirement. page 63 Appendix 2. Definitions of Stage 3 Opportunistic Illness in HIV page 66 Appendix 3. Schedule of Assessments page 69 Appendix 4. DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event page 73 Appendix 5. Management of Clinical and Laboratory Adverse Event page 101 | |
dc.language.iso | en | |
dc.title | 針對HIV感染者使用固定劑量併用製劑Bictegravir/Emtricitabine/Tenofovir Alafenamide的療效與安全性的統合分析與臨床試驗計畫書 | zh_TW |
dc.title | Meta-Analysis of Efficacy and Safety of Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Among People Living with HIV and clinical trial protocol | en |
dc.type | Thesis | |
dc.date.schoolyear | 110-2 | |
dc.description.degree | 碩士 | |
dc.contributor.author-orcid | 0000-0002-7362-0708 | |
dc.contributor.oralexamcommittee | 楊宏志(Hung-Chih Yang),孫幸筠(Hsin-Yun Sun) | |
dc.subject.keyword | 不良反應,bictegravir/emtricitabine/tenofovir alafenamide,高效能抗愛滋病毒治療,HIV嵌入酶鏈轉移抑制劑,隨機分配試驗,持續性病毒反應, | zh_TW |
dc.subject.keyword | adverse effects,bictegravir/emtricitabine/tenofovir alafenamide,highly active antiretroviral therapy,HIV integrase inhibitor,randomized controlled trial,sustained virologic response, | en |
dc.relation.page | 133 | |
dc.identifier.doi | 10.6342/NTU202201437 | |
dc.rights.note | 同意授權(限校園內公開) | |
dc.date.accepted | 2022-07-26 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
dc.date.embargo-lift | 2022-10-03 | - |
顯示於系所單位: | 臨床醫學研究所 |
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