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依曲韦林作为HIV RNA抑制患者的换药选择:近期试验综述

Etravirine as a Switching Option for Patients with HIV RNA Suppression: A Review of Recent Trials.

作者信息

Nelson Mark, Hill Andrew, van Delft Yvon, Moecklinghoff Christiane

机构信息

Chelsea and Westminster Hospital, St. Stephens Centre, London SW10 9NH, UK.

Janssen Research and Development, High Wycombe HP12 4DP, UK.

出版信息

AIDS Res Treat. 2014;2014:636584. doi: 10.1155/2014/636584. Epub 2014 Feb 25.

Abstract

Unlike other nonnucleoside reverse transcriptase inhibitors, etravirine is only approved for use in treatment-experienced patients. In the DUET 1 and 2 trials, 1203 highly treatment-experienced patients were randomized to etravirine or placebo, in combination with darunavir/ritonavir and optimized background treatment. In these trials, etravirine showed significantly higher rates of HIV RNA suppression when compared with placebo (61% versus 40% at Week 48). There was no significant rise of lipids or neuropsychiatric adverse events, but there was an increase in the risk of rash with etravirine treatment. In the SENSE trial, which evaluated etravirine and efavirenz in 157 treatment-naïve patients in combination with 2 nucleoside analogues, there was a lower risk of lipid elevations and neuropsychiatric adverse events with etravirine when compared to efavirenz. Etravirine has been evaluated in three randomized switching studies. In the SSAT029 switch trial, 38 patients who had neuropsychiatric adverse events possibly related to efavirenz showed an improvement in these after switching to etravirine. The Swiss Switch-EE recruited 58 individuals without neuropsychiatric adverse events who were receiving efavirenz, and no benefit was shown when switching to etravirine. In the Spanish ETRA-SWITCH trial (n = 46), there were improvements in lipids when individuals switched from a protease inhibitor to etravirine. These switching trials were conducted in patients with full HIV RNA suppression: <50 copies/mL and with no history of virological failure or resistance to therapy. The results from these three randomized switching studies suggest a possible new role for etravirine, in combination with two nucleoside analogues, as a switching option for those with HIV RNA suppression but who are reporting adverse events possibly related to antiretroviral therapy. However a large well-powered trial would need to be conducted to strengthen the evidence from the pilot studies conducted so far.

摘要

与其他非核苷类逆转录酶抑制剂不同,依曲韦林仅被批准用于有治疗经验的患者。在DUET 1和2试验中,1203名有高度治疗经验的患者被随机分为依曲韦林组或安慰剂组,同时联合使用达芦那韦/利托那韦及优化的背景治疗。在这些试验中,与安慰剂相比,依曲韦林在第48周时显示出显著更高的HIV RNA抑制率(61%对40%)。脂质或神经精神方面的不良事件没有显著增加,但依曲韦林治疗会增加皮疹风险。在SENSE试验中,对157名初治患者联合2种核苷类似物评估依曲韦林和依非韦伦,与依非韦伦相比,依曲韦林导致脂质升高和神经精神不良事件的风险更低。依曲韦林已在三项随机换药研究中进行了评估。在SSAT029换药试验中,38名可能与依非韦伦相关的神经精神不良事件患者在换用依曲韦林后症状有所改善。瑞士Switch-EE招募了58名正在接受依非韦伦治疗且无神经精神不良事件的患者,换用依曲韦林后未显示出益处。在西班牙ETRA-SWITCH试验(n = 46)中,患者从蛋白酶抑制剂换用依曲韦林后脂质情况有所改善。这些换药试验是在HIV RNA完全抑制(<50拷贝/mL)且无病毒学失败或治疗耐药史的患者中进行的。这三项随机换药研究的结果表明,依曲韦林联合两种核苷类似物可能对那些HIV RNA得到抑制但报告有可能与抗逆转录病毒治疗相关不良事件的患者具有新的换药选择作用。然而,需要进行一项大规模、有力的试验来加强目前这些初步研究所得出的证据。

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