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[新分子在抗逆转录病毒治疗中的作用。拉替拉韦的地位]

[Role of the new molecules in antiretroviral therapy. Position of raltegravir].

作者信息

Arribas José R

机构信息

Consulta de Medicina Interna II (Unidad VIH), Hospital La Paz, Madrid, España.

出版信息

Enferm Infecc Microbiol Clin. 2008 Nov;26 Suppl 12:53-9. doi: 10.1016/s0213-005x(08)76574-1.

Abstract

Antiretroviral rescue therapy has been revolutionized by the development of new drugs in the last few years: enfuvirtide (a fusion inhibitor), tipranavir/ritonavir (a high genetic barrier protease inhibitor), darunavir/ritonavir (a high genetic barrier protease inhibitor), etravirine (a non-nucleoside reverse transcriptase inhibitor active against nevirapine- and efavirenz- resistant HIV), maraviroc (a CCR5 coreceptor inhibitor) and raltegravir (an integrase inhibitor). The use of these drugs in rescue regimens has allowed the goal of antiretroviral rescue therapy to be the same as that in treatment naive-patients: to achieve a viral load lower than 50 copies of RNA of HIV/ml. Raltegravir is the first integrase inhibitor available for clinical use in Spain. This drug is primarily metabolized through UGT1A1-mediated glucuronidation and consequently has a low potential for interactions with drugs metabolized by the cytochrome P450 pathway. Raltegravir has been demonstrated to have high efficacy in two large clinical trials of rescue therapy, especially when combined with darunavir/ritonavir and enfuvirtide. Preliminary data suggest that raltegravir could also be an effective drug in treatment-naive patients and as substitution therapy in patients with toxicity due to boosted protease inhibitor therapy. The drug's unusual mechanism of action has reopened the possibility of a positive effect on latent HIV reservoirs.

摘要

在过去几年中,新型药物的研发彻底改变了抗逆转录病毒挽救治疗:恩夫韦肽(一种融合抑制剂)、替拉那韦/利托那韦(一种具有高基因屏障的蛋白酶抑制剂)、达芦那韦/利托那韦(一种具有高基因屏障的蛋白酶抑制剂)、依曲韦林(一种对奈韦拉平和依法韦仑耐药的HIV有效的非核苷类逆转录酶抑制剂)、马拉维罗克(一种CCR5共受体抑制剂)和拉替拉韦(一种整合酶抑制剂)。在挽救治疗方案中使用这些药物,使抗逆转录病毒挽救治疗的目标与初治患者相同:将病毒载量降至低于每毫升50拷贝的HIV RNA。拉替拉韦是西班牙首个可用于临床的整合酶抑制剂。该药物主要通过UGT1A1介导的葡萄糖醛酸化进行代谢,因此与通过细胞色素P450途径代谢的药物发生相互作用的可能性较低。在两项大型挽救治疗临床试验中已证明拉替拉韦具有高效性,尤其是与达芦那韦/利托那韦和恩夫韦肽联合使用时。初步数据表明,拉替拉韦在初治患者中也可能是一种有效的药物,并且可作为因蛋白酶抑制剂强化治疗而出现毒性的患者的替代治疗药物。该药物不同寻常的作用机制重新开启了对潜伏HIV储存库产生积极影响的可能性。

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