三种抗逆转录病毒方案治疗 HIV-1 初治的疗效和安全性：多种族多国环境下的随机临床试验。

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

机构信息

Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, United States of America.

出版信息

PLoS Med. 2012;9(8):e1001290. doi: 10.1371/journal.pmed.1001290. Epub 2012 Aug 14.

DOI:10.1371/journal.pmed.1001290

PMID:22936892

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3419182/

Abstract

BACKGROUND

Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.

METHODS AND FINDINGS

1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).

CONCLUSION

EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.

TRIAL REGISTRATION

www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

摘要

背景

在资源有限的环境中，需要简化剂量和提高安全性的抗逆转录病毒方案，以最大限度地提高抗逆转录病毒的效率。我们研究了每日一次与每日两次剂量的抗逆转录病毒方案在世界不同地区的疗效和安全性。

方法和发现

来自四大洲 9 个国家的 1571 名 HIV-1 感染者（47%为女性），以相等的概率被分配接受依非韦伦加拉米夫定-齐多夫定（EFV+3TC-ZDV）、阿扎那韦加多替拉韦-恩曲他滨（ATV+DDI+FTC）或依非韦伦加恩曲他滨-替诺福韦酯富马酸（EFV+FTC-TDF）的开放性标签抗逆转录病毒治疗。假设 ATV+DDI+FTC 和 EFV+FTC-TDF 与 EFV+3TC-ZDV 相比非劣效，如果在 30%的参与者出现治疗失败的情况下，风险比（HR）的上限单侧 95%置信区间（CI）≤1.35。在累积 472 例治疗失败之前，独立监测委员会建议停止研究随访。在中位随访 184 周期间，526 名接受 EFV+FTC-TDF 治疗的参与者中有 95 例（18%）发生治疗失败，而 519 名接受 EFV+3TC-ZDV 治疗的参与者中有 98 例（19%）发生治疗失败（HR 0.95，95%CI 0.72-1.27；p=0.74）。与 EFV+3TC-ZDV 相比，在接受 EFV+FTC-TDF 治疗的 243 名（46%）参与者中发生了 313 名（60%）接受 EFV+3TC-ZDV 治疗的参与者（HR 0.64，CI 0.54-0.76；p<0.001），并且方案安全性在性别之间存在显著交互作用（女性为 0.50，CI 0.39-0.64；男性为 0.79，CI 0.62-1.00；p=0.01）。在中位随访 81 周期间，在接受 ATV+DDI+FTC 治疗的 526 名参与者中有 108 例（21%）发生治疗失败，而在接受 EFV+3TC-ZDV 治疗的 519 名参与者中有 76 例（15%）发生治疗失败（HR 1.51，CI 1.12-2.04；p=0.007）。

结论

在这个试验人群中，与 EFV+3TC-ZDV 相比，EFV+FTC-TDF 具有相似的高疗效，该试验人群在多个跨国环境中招募。EFV+FTC-TDF 的安全性更高，特别是在 HIV-1 感染的女性中，以及每日一次的 EFV 剂量，这对在资源有限的国家中使用这种方案进行 HIV-1 感染的初始治疗是有利的。ATV+DDI+FTC 的疗效较差，不推荐作为初始抗逆转录病毒方案。