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標題: | 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 Efficacy and Tolerability of Dolutegravir (DTG) Based Antiretroviral Therapy Compared to Other Combination Antiretroviral Therapy for HIV-Positive Patients: A Meta-Analysis |
作者: | Fan Chi Kit 范志杰 |
指導教授: | 方啟泰(Chi-Tai Fang) |
關鍵字: | 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, human immunodeficiency virus (HIV),antiretroviral therapy (ART),dolutegravir (DTG),efficacy,tolerability, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78650 |
DOI: | 10.6342/NTU201902988 |
全文授權: | 有償授權 |
顯示於系所單位: | 公共衛生碩士學位學程 |
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