The Kirby Institute, University of New South Wales, Sydney, Australia.
AIDS Res Ther. 2013 Dec 13;10(1):33. doi: 10.1186/1742-6405-10-33.
The nucleoside(tide) reverse transcriptase inhibitors (NRTIs) have traditionally been an important 'back-bone' of an antiretroviral therapy (ART) regimen. However all agents have been associated with both short- and long-term toxicity. There have also been concerns regarding the efficacy and safety of a treatment sequencing strategy in which those with past exposure and/or resistance to one or more NRTIs are re-exposed to 'recycled' NRTIs in subsequent ART regimens. Newer, potent and possible safer, agents from various ART classes continue to become available. There has therefore been growing interest in evaluating NRTI-sparing regimens. In this review, we examined studies of NRTI-sparing regimens in adult HIV-positive patients with varying degrees of ART experience. We found that in treatment experienced patients currently on a failing regimen with detectable viral load, there now exists a robust evidence for the use of NRTI-sparing regimens including raltegravir with a boosted-protease inhibitor with or without a third agent. In those on a virologically suppressive regimen switching to a NRTI-sparing regimen or in those ART-naïve patients initiating an NRTI-sparing regimen, evidence is sparse and largely comes from small exploratory trials or observational studies. Overall, these studies suggest that caution needs to be exercised in carefully selecting the right candidate and agents, especially in the context of a dual-therapy regimen, to minimise the risks of virological failure. There is residual toxicity conferred by the ritonavir boost in protease-inhibitor containing NRTI-sparing regimens. Fully-powered studies are needed to explore the place of N (t)RTI-sparing regimens in the sequencing of ART. Additionally research is required to explore how to minimise the adverse effects associated with ritonavir-based pharmacoenhancement.
核苷（酸）逆转录酶抑制剂（NRTIs）一直是抗逆转录病毒疗法（ART）方案的重要“骨干”。然而，所有这些药物都与短期和长期毒性有关。人们还担心在一种治疗方案中，那些过去接触过或对一种或多种 NRTI 有耐药性的人会再次接触到后续 ART 方案中“回收”的 NRTI 的疗效和安全性。来自不同 ART 类别的更新、更有效和可能更安全的药物不断推出。因此，人们对评估 NRTI 节省方案的兴趣日益浓厚。在这篇综述中，我们检查了不同 ART 经验水平的 HIV 阳性成年患者中 NRTI 节省方案的研究。我们发现，对于目前正在接受失败方案治疗且病毒载量可检测的治疗经验丰富的患者，现在有强有力的证据支持使用 NRTI 节省方案，包括与增强型蛋白酶抑制剂联合使用或不联合第三种药物的拉替拉韦。对于那些正在接受病毒学抑制治疗的患者，切换到 NRTI 节省方案，或者对于那些新开始 NRTI 节省方案的患者，证据很少，主要来自小型探索性试验或观察性研究。总的来说，这些研究表明，在仔细选择合适的候选药物和药物时需要谨慎，特别是在双重治疗方案的情况下，以最大限度地降低病毒学失败的风险。在包含 NRTI 节省方案的蛋白酶抑制剂中，利托那韦增强会带来残留毒性。需要进行充分的研究来探讨 N（t）RTI 节省方案在 ART 方案中的位置。此外，还需要研究如何最大限度地减少与基于利托那韦的药物增强相关的不良反应。
