主页/艾滋治疗与生活/HIV简化治疗,势在必行

HIV简化治疗,势在必行

简化治疗是指可以维持病毒抑制,并减少药物的不良反应并将治疗药物简化的方案。简化治疗也可以一定程度上减少药物的不良反应,提高依从性,降低医疗成本。

艾滋病从鸡尾酒疗法问世以来,已经得到了良好的控制,但是目前常见的三联方案,随着治疗时间的延长,在不同人身上也出现了因人而异的副作用,或是依从性难以把控。

简化治疗是指可以维持病毒抑制,并减少药物的不良反应并将治疗药物简化的方案。简化治疗也可以一定程度上减少药物的不良反应,提高依从性,降低医疗成本。

从目前研究可以看出,部分简化治疗方案可以达到维持病毒抑制,同时减少了药物的不良反应,并减少了药物间叠加的不良反应,提高了患者依从性和便利性。

目前简化治疗方面的研究,主要包括双药治疗、单药治疗和间歇治疗方案。

今天 我们就来谈谈 HIV的简化治疗

 

 双药治疗方案

双核苷类反转录酶抑制剂

从1987年第一个抗反转录病毒药物获得批准,到开始三联 haart方案推广普及,历经了10年。

从那时起,抗病毒治疗指导方针便一直建议HIV感染者坚持使用三联疗法。之前常用的双核苷类反转录酶抑制剂治疗方案,在三联“上位“后,便被打入了“冷宫”,但依旧有相当一部分感染者受益于双核苷反转录酶抑制剂疗法。

研究发现:虽然三联药物在抑制病毒方面效果更好。但是,在基线病毒载量低于3×10^4 cp/ml的感染者中,两种方案并没有明显的差异。有研究表示,具有高cd4和低病载量(范围在1×103~3×104拷贝/ml)的初治患者,使用替诺福韦、恩曲他滨(TDF+emtricitabine FTC),4周内达到了病毒学抑制,与三联方案并没有统计学上的差异,且没有严重的不良反应发生。

TDF/FTC专利将很快结束。TDF/FTC很可能成为初治感染者一线治疗方案的的骨干药物之一。

蛋白酶抑制剂联合拉米夫定应用

提升抗病毒治疗的效果,需要的是提升药物的效力,并抑制病毒的突变可能。

蛋白酶抑制剂也许也是一种理想的选择。

有学者实验对比了LPV/r+3TC与LPV/r+3TC+nr-tis两种方案的效果。结果显示,初治患者双药的抗病毒效果比起标准的三联药物治疗方案并不差,无论基线病载量处于什么水平,在48周抗病毒治疗后,分别有88.3%和83.7%的感染者获得了病毒抑制[HIV核糖核酸(rna)<50 cp/ml],其中有的患者基线病毒载量超过了1×10^5拷贝/ml。

该研究中,在治疗过程中很少出现严重的药物不良反应,并且该治疗方案耐药发生的风险极低,耐受性也很好。因此,这项研究被认为是开创了抗病毒药物减负方案的先例。

另一项研究表明,在取得病毒抑制半年后分为两组,一组使用LPV/r+3TC,一组继续使用原方案,即LPV/r+3TC+NRTIs。经过48周的抗病毒治疗后发现,LPV/r+3TC的组合方案抗病毒效果相较于标准的三联治疗方案也并不差。

蛋白酶抑制剂联合整合酶抑制剂

蛋白酶抑制剂联合整合酶抑制剂的优势是保留核苷类反转录酶抑制剂的应用,两者的联合不会发生药物间的不良反应叠加,这可能会为那些因长期服用核苷类反转录酶抑制剂而发生不良反应(如脂肪萎缩、疲劳和/或轻度肾功能不全)的患者提供了一个更具吸引力的选择。

蛋白酶抑制剂(达芦那韦/利托那韦arunavir/rDRV/r)联合 (拉替拉韦RaltegravirRAL) 

研究指出DRV/r+RAL效果并不如预期好,分析失败的原因可能和高病毒载量有关。不过研究也报告说,DRV/r+RAL的方案可能对于 HIV RNA<1×10^5 cd4=””>200个/μl 的感染者效果并不差。

洛匹那韦/利托那韦+拉替拉韦(LPV/r+ RAL)

研究表明,经过48周的治疗,LPV/r+RAL双药组合并不比传统的包含NRTI为骨干的三联药物效果差,其安全性和耐受性也更好。另有试验结果也提示,LPV/r+RAL双药组合的病毒学抑制好于LPV/r+TDF/FTC。一组对经 HAART后转换为LPV/r+RAL治疗方案的患者的研究表示,经过48周的治疗后,与标准三联治疗组对比,发现两组病毒学抑制率及安全性相当。

阿扎那韦/利托那韦+拉替拉韦(aTV/r+RAL)

有研究对比了aTV+RAL方案与aTV/r+TDF/FTC方案,尽管两个方案抗病毒疗效相似,但aTV+RAL方案中由于aTV出现了严重的高胆红素血症及RAL耐药率较高,致使实验提前终止。故目前美国青少年及成人抗病毒治疗指南也不推荐这一组合。

蛋白酶抑制剂联合非核苷类反转录酶抑制剂

LPV/r+NVP对比 NVP+ZDV/3TC或LPV/r+ ZDV/3TC组,前者达到病毒学抑制的概率稍低,且LPV/r+ NVP组合发生皮疹等不良反应的概率更高一些。故需要进一步探讨该简化方案是否可行。

蛋白酶抑制剂联合马拉韦罗(maravirocMVC)

因ATV/r+MVC组对比ATV/r+TDF/FTC组,分别有36.7%和19.7%的患者出现了3~4级高胆红素血症。且应用DRV/r+MVC,结果发生病毒学失败的概率很高,尤其病载量较高的携带者,在48周之后仍有16.7%(4/24)的患者没有达到病毒学抑制。

整合酶抑制剂联合拉米夫定

多替拉韦(dolutegravir,DTG)是一个高效的整合酶抑制剂,它的特点是拥有高基因耐药屏障,联合拉米夫定这种耐受性好并且常用的核苷酸反转录酶抑制剂,是一种极具吸引力的组合。然而,到目前为止,只有很少的研究数据支持这样的组合。有研究结果表明,104例患者使用这两种药物的组合,其中101例患者达到病毒学抑制(97.1%)。

整合酶抑制剂联合非核苷类反转录酶抑制剂

不包含核苷类反转录酶抑制剂与蛋白酶抑制剂的方案的优点是,几乎不会发生代谢不良事件,没有线粒体毒性,对骨骼和肾脏的影响最小。这些不良反应最常发生于老年患者或就医条件差的患者中。90%的患者达到了病毒的持续抑制。病毒学反弹只发生在既往对非核苷类反转录酶抑制剂耐药的患者。

相关方面的实验正在进行(nct02212379)中,研究将评价45岁以上老年人应用这种组合治疗的疗效,结果有望近期知晓。

 

单药方案

蛋白酶抑制剂单一疗法

大约在10年前就有研究提出,LPV/r单药是否可以作为对那些病毒量低于1×105拷贝/ml、CD4细胞计数超过100个/μl初治患者的治疗方案,并达到有效地抑制病毒作用。

但是单药治疗增加了失败的风险。从目前的观点来看蛋白酶抑制剂,比如达芦那韦(darunavir),即使没有被推荐作为单药治疗,但仍表现出高效的抗病毒潜力。

 

 

多替拉韦(dolutegravir)单一疗法

多替拉韦作为整合酶抑制剂,与蛋白酶抑制剂合用可以增强抗病毒效果,提高病毒抑制率,且具有高耐药基因屏障。

但是实验结果并不是那么乐观,相当一部分人群出现了耐药,或者病载量的反弹。

由于单药治疗仍存在耐药而增加了失败的风险,故目前不推荐单药治疗。

间歇疗法

一直在寻找一种可以减少药物使用时间,并能达到持续的病毒抑制的方法,那就是间歇用药。有研究首先提出了治疗7天停药7天的抗病毒治疗方案。但在一项成人的抗病毒的研究中发现,这种间歇治疗方案对比持续治疗方案,抗病毒效果并不显著,并且有耐药发生。

可能因为一个星期的停药时间太长。有研究表明,缩短停药的时间,如周末(2天)或3天的间歇期可能是一个更好的选择。

有试验入组了199例儿童患者,这些儿童应用一线抗病毒药物包括两种核苷类似物联合依非韦伦,对比间歇疗法(5天治疗,2天停药)与连续疗法,结果显示抗病毒疗效并不差。

简化抗病毒治疗方案是在不影响疗效,即达到持续几十年甚至长期的病毒抑制的前提下,临床医生使用尽量少的药物,缩短了药物的治疗时间,减轻了药物单独和叠加的毒性风险,减轻了患者的经济负担。它是当前抗病毒治疗的下一个目标,也是目前抗病毒治疗面临的最大的挑战之一。当然,并不是每一位感染者都适合简化抗病毒治疗。

当然,对于简化治疗其长期疗效仍有待于进一步观察和评估。期望简化治疗方案能开辟艾滋病抗病毒治疗的新领域。

随着对艾滋病病毒(HIV)致病机理认识的不断提高,治疗药物的更新,全球HIV感染者抗病毒治疗领域已经有了相当大的进步。

今年的第22届世界艾滋病大会上发布的研究提示,通过坚持治疗,获得病毒抑制后可以完全阻断性传播这一途径。

在当前尚没有办法完全治愈艾滋病的前提下,抗病毒治疗是抑制HIV传播最佳办法之一。

对于阴性群体来说,做好预防手段,依旧尤为重要。

 

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