Has the time come to abandon efavirenz for first-line antiretroviral therapy?
Has the time come to abandon efavirenz for first-line antiretroviral therapy?
复制标题
是时候放弃依非韦伦而采用一线抗逆转录病毒治疗了吗？
DOI：
10.1093/jac/dku058
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
M. Wainberg
中科院分区：
文献类型：
--
作者：
F. Raffi;A. Pozniak;M. Wainberg
Efavirenz作为首选的第三种药物，与两种核苷类药物一起用于一线联合抗逆转录病毒治疗（ART）已有近15年的历史。依非韦伦的固定剂量组合使得它非常有吸引力。然而，由于(i)与efavirenz相关的不良事件，（ii）与较新的抗逆转录病毒药物相比，efavirenz的总体疗效较差，（iii） efavirenz被FDA列为妊娠类D类，（iv）传播性耐药突变的患病率相对较高，有必要重新考虑efavirenz在一线抗逆转录病毒治疗中的作用。我们回顾了现有的证据，这些证据挑战了依非韦伦目前在一线HIV治疗指南中的地位。除了其潜在的动物致畸性和与使用相关的中度神经精神不良事件外，最近与其他抗逆转录病毒药物相比，efavirenz与自杀风险增加有关。最重要的是，在未接受抗逆转录病毒治疗的患者中，efavirenz的总体疗效低于各种比较药物，包括利匹韦林、雷替格拉韦和多替格拉韦。此外，流行病学数据表明，在世界各地，非核苷类逆转录酶抑制剂耐药的患病率已达到5%-8%，少数传播的非核苷类逆转录酶抑制剂耐药相关突变可能对一线依非韦伦抗逆转录病毒治疗的结果产生负面影响。基于对疗效、毒性和耐药性的考虑，是时候重新考虑在抗逆转录病毒治疗中常规使用依非韦伦了。当然，这是以有其他抗逆转录病毒药物可以替代依非韦伦为前提的，而且在某些发展中国家可能不适用，因为情况并非如此。
Efavirenz has been recommended as a preferred third agent together with two nucleos(t)ides for first-line combination antiretroviral therapy (ART) for >15 years. The availability of efavirenz in a fixed-dose combination makes it very attractive. However, because of (i) adverse events associated with efavirenz, (ii) a poorer overall efficacy of efavirenz compared with newer antiretrovirals, (iii) the ranking of efavirenz as FDA Pregnancy Category D and (iv) the relatively high prevalence of transmitted drug-resistance mutations, there is a need to reconsider the role of efavirenz in first-line ART. We review the available evidence that challenges efavirenz's current position in first-line HIV treatment guidelines. Apart from its animal teratogenic potential, and moderate neuropsychiatric adverse events associated with its use, efavirenz has recently been associated with an increased risk of suicidality when compared with other antiretroviral drugs. Most importantly, efavirenz has demonstrated overall inferior efficacy to various comparator drugs, which include rilpivirine, raltegravir and dolutegravir, in antiretroviral-naive patients. Furthermore, epidemiological data indicate that the prevalence of non-nucleoside reverse transcriptase inhibitor resistance has reached 5%-8% in various parts of the world, and minority transmitted non-nucleoside reverse transcriptase inhibitor resistance-associated mutations can have a negative impact on the outcome of first-line efavirenz-based ART. Based on considerations of efficacy, toxicity and resistance, it is time to reconsider the routine use of efavirenz in ART. This, of course, presupposes that other antiretrovirals will be available in place of efavirenz, and may not be applicable in certain developing country settings where this is not the case.
DOI：
--
发表时间：
2011
期刊：
--
影响因子：
--
作者：
R. Paredes;H. Ribaudo;E. Svarovskaia;K. Metzner;M. Kozal;K. H. Hullsiek;M. Balduin;M. Jakobsen;A. Geretti;R. Thiébaut;L. Ostergaard;B. Masquelier;Jeffrey A Johnson;Michael D. Miller;D. Kuritzkes
通讯作者：
R. Paredes;H. Ribaudo;E. Svarovskaia;K. Metzner;M. Kozal;K. H. Hullsiek;M. Balduin;M. Jakobsen;A. Geretti;R. Thiébaut;L. Ostergaard;B. Masquelier;Jeffrey A Johnson;Michael D. Miller;D. Kuritzkes
影响因子：
158.5
作者：
Robbins, GK;De Gruttola, V;Doolan, A
通讯作者：
Doolan, A