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台湾地区第一代蛋白酶抑制剂病毒学治疗失败患者中出现的HIV-1对替拉那韦和达芦那韦的耐药性

Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan.

作者信息

Hsieh S-M, Chang S-Y, Hung C-C, Sheng W-H, Chen M-Y, Chang S-C

机构信息

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan UniversityCollege of Medicine, Taipei, Taiwan.

出版信息

Int J STD AIDS. 2011 Nov;22(11):617-20. doi: 10.1258/ijsa.2009.009007.

DOI:10.1258/ijsa.2009.009007
PMID:22096044
Abstract

Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (PIs). Whether the HIV-1 from these patients with virological failure to first-generation PIs remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation PIs in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 PIs. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation PIs.

摘要

利托那韦增强的替拉那韦(TPV/r)和达芦那韦(DRV/r)已被批准用于对多种蛋白酶抑制剂(PI)产生病毒学耐药的患者。第一代PI病毒学治疗失败患者体内的HIV-1对TPV/r或DRV/r是否仍敏感,这是个问题。分析了三个时间段内经历病毒学治疗失败患者的HIV-1分离株对第二代PI的敏感性:2006年9月至2007年4月(第1阶段)、2007年5月至2007年12月(第2阶段)和2008年1月至2008年8月(第3阶段)。共纳入53名受试者,51名受试者的分离株(96.2%)对≥1种PI耐药。从第1阶段到第3阶段,TPV和DRV的突变分数以及对TPV或DRV耐药的分离株百分比显著增加。我们的数据显示,在过去两年中,第一代PI病毒学治疗失败的患者对TPV和DRV的基因型耐药水平显著增加。

相似文献

1
Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan.台湾地区第一代蛋白酶抑制剂病毒学治疗失败患者中出现的HIV-1对替拉那韦和达芦那韦的耐药性
Int J STD AIDS. 2011 Nov;22(11):617-20. doi: 10.1258/ijsa.2009.009007.
2
Virologic and immunologic effectiveness of tipranavir/ritonavir (TPV/r)- versus darunavir/ritonavir (DRV/r)-based regimens in clinical practice.在临床实践中,替拉那韦/利托那韦(TPV/r)与达芦那韦/利托那韦(DRV/r)方案的病毒学和免疫学有效性。
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Changes in darunavir/r resistance score after previous failure to tipranavir/r in HIV-1-infected multidrug-resistant patients.在先前使用替拉那韦/利托那韦治疗失败的HIV-1感染多药耐药患者中,达芦那韦/利托那韦耐药评分的变化
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Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure.一线蛋白酶抑制剂对病毒学治疗失败的HIV-1感染患者中替拉那韦预测耐药性的影响。
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Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial.在治疗经验丰富的患者中,普泽那韦联合利托那韦与达芦那韦的比较:来自随机 POTENT 试验的观察性数据。
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Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir.在使用达芦那韦治疗失败的蛋白酶抑制剂(PI)经治患者中,与选择对PI产生耐药性的突变相关的因素。
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Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen.在接受含达芦那韦治疗方案但治疗失败的患者中,新出现的耐药突变模式及影响
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Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance.替拉那韦:首个用于治疗蛋白酶耐药性的非肽类蛋白酶抑制剂。
Clin Ther. 2007 Nov;29(11):2309-18. doi: 10.1016/j.clinthera.2007.11.007.
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Evidence for different susceptibility to tipranavir and darunavir in patients infected with distinct HIV-1 subtypes.感染不同HIV-1亚型的患者对替拉那韦和达芦那韦敏感性不同的证据。
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引用本文的文献

1
Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.基于替诺福韦/利托那韦或达芦那韦/利托那韦方案的抗逆转录病毒治疗经验的 HIV-1 患者的病毒学应答:一项随机对照临床试验的荟萃分析和荟萃回归。
PLoS One. 2013 Apr 4;8(4):e60814. doi: 10.1371/journal.pone.0060814. Print 2013.
2
Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1.替拉那韦(TPV)失去蛋白酶二聚抑制活性及其与 HIV-1 对 TPV 耐药性获得的关系。
J Virol. 2012 Dec;86(24):13384-96. doi: 10.1128/JVI.07234-11. Epub 2012 Sep 26.