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[马拉维若及其他CCR5拮抗剂治疗的次要效应。CCR5阻断剂的潜在影响]

[Secondary effects of treatment with maraviroc and other CCR5 antagonists. Potential impact of the CCR5 blocker].

作者信息

Arribas López 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 Oct;26 Suppl 11:23-7. doi: 10.1016/s0213-005x(08)76560-1.

Abstract

Maraviroc is the first inhibitor of CCR5 co-receptors to be marketed as an antiretroviral. The pre-clinical studies and phase III trials have shown that it has a very favourable safety profile. No characteristic adverse effect of maraviroc has been identified. Unlike with aplaviroc, where its clinical development was stopped due to serious hepatoxicity, no increase in liver toxicity has been demonstrated in patients treated with maraviroc even if they are co-infected by hepatotropic virus. Nor was there any evidence of an increase in the incidence of neoplasms or serious infections in patients treated with maraviroc. In a study on naive patients, maraviroc produced nonsignificant changes in total cholesterol, LDL, HDL and triglycerides. Although CCR5 co-receptors play a role in the immune response of the body, it has not been shown whether individuals homozygote for its deletion (delta-32 mutation) have an increased risk of serious infections, with the possible exception of encephalitis due to the West Nile virus. However, long-term follow up is required on patients treated with to be able to rule out any increased susceptibility to infections or neoplasms.

摘要

马拉维若(maraviroc)是首个作为抗逆转录病毒药物上市的CCR5共受体抑制剂。临床前研究和III期试验表明,其安全性非常良好。尚未发现马拉维若有任何特征性不良反应。与阿扑拉维若(aplaviroc)不同,后者因严重肝毒性而停止临床开发,而使用马拉维若治疗的患者,即使合并嗜肝病毒感染,也未显示肝毒性增加。也没有证据表明使用马拉维若治疗的患者肿瘤发生率或严重感染发生率增加。在一项针对初治患者的研究中,马拉维若对总胆固醇、低密度脂蛋白、高密度脂蛋白和甘油三酯产生的变化无统计学意义。尽管CCR5共受体在机体免疫反应中起作用,但尚未表明其缺失的纯合子个体(Δ32突变)是否有严重感染风险增加,西尼罗河病毒脑炎可能除外。然而,需要对接受治疗的患者进行长期随访,以便排除对感染或肿瘤的易感性增加。

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