Palella Frank J, Fisher Martin, Tebas Pablo, Gazzard Brian, Ruane Peter, Van Lunzen Jan, Shamblaw David, Flamm Jason, Ebrahimi Ramin, Porter Danielle, White Kirsten, Hindman Jason, Elbert Elizabeth, De-Oertel Shampa, Fralich Todd
aNorthwestern University, Feinberg School of Medicine, Chicago, Illinois, USA bBrighton and Sussex University Hospitals, Brighton, UK cUniversity of Pennsylvania, Division of Infectious Diseases, Clinical Trials Unit, Philadelphia, Pennsylvania, USA dChelsea and Westminster Hospital Foundation Trust, London, UK ePeter Ruane, MD, Inc., Los Angeles, California, USA fUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany gLa Playa Medical Group and Clinical Research, San Diego hKaiser Permanente, Sacramento iGilead Sciences Inc., Foster City, California, USA.
AIDS. 2014 Jan 28;28(3):335-44. doi: 10.1097/QAD.0000000000000087.
To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants.
Phase 3b, randomized, open-label, international, 48-week switch study.
Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis.
A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval -1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group.
Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.
评估在病毒学抑制的HIV-1感染参与者中，将基于利托那韦增强型蛋白酶抑制剂的方案[蛋白酶抑制剂+利托那韦+两种核苷（酸）逆转录酶抑制剂（NRTIs）；研究入组前暴露≥6个月且无既往治疗失败]简化为单片复方制剂（STR）rilpivirine/恩曲他滨/替诺福韦酯（RPV/FTC/TDF）的疗效和安全性。
3b期、随机、开放标签、国际性、为期48周的转换研究。
参与者按2∶1随机分组，立即转换为RPV/FTC/TDF或继续使用其基线蛋白酶抑制剂+利托那韦+2种NRTIs方案，并在第24周延迟转换为RPV/FTC/TDF。主要终点是通过快照分析，在第24周时RPV/FTC/TDF与蛋白酶抑制剂+利托那韦+两种NRTIs相比，维持血浆HIV-1 RNA低于50拷贝/ml的非劣效性（12%的界值）。
共有476名参与者被随机分组并接受了至少一剂研究药物。两组间的人口统计学和基线特征相似。达到了第24周非劣效性的主要目标：通过快照分析，RPV/FTC/TDF组93.7%的参与者HIV-1 RNA低于50拷贝/ml，蛋白酶抑制剂+利托那韦+两种NRTIs组为89.9%（差异3.8%，95%置信区间-1.6至9.1%）。至第48周，立即转换组89.3%的参与者维持了病毒学抑制。无论参与者抗逆转录病毒治疗前的HIV-1 RNA水平如何，RPV/FTC/TDF均维持了较高的抑制率。转换为RPV/FTC/TDF后耐药突变的总体发生率较低。RPV/FTC/TDF接受者的总胆固醇、低密度脂蛋白（LDL）和甘油三酯的降低幅度显著大于蛋白酶抑制剂+利托那韦+两种NRTIs组。
在病毒学抑制的HIV-1感染参与者中，从利托那韦增强型蛋白酶抑制剂方案转换为STR RPV/FTC/TDF可维持病毒学抑制，病毒学失败风险低，同时改善总胆固醇、LDL和甘油三酯。
