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。