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

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。

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.