Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors
复制标题
蛋白酶抑制剂治疗的测序：对蛋白酶抑制剂失败的患者的 HIV 表型耐药性分析的见解
DOI：
10.1097/00002030-200103300-00010
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发表时间：
2001
期刊：
影响因子：
3.8
通讯作者：
R. Haubrich
中科院分区：
文献类型：
--
作者：
C. Kemper;M. Witt;Phillip H. Keiser;M. Dubé;D. Forthal;M. Leibowitz;D. Smith;A. Rigby;N. Hellmann;Y. Lie;J. Leedom;D. Richman;J. McCutchan;R. Haubrich
目的研究HIV-1蛋白酶抑制剂治疗失败患者对蛋白酶抑制剂的敏感性。抗逆转录病毒易感性的横断面分析。在六个大都市设立艾滋病诊所。患者88例HIV RNA > 400拷贝/ml的HIV感染成人，经过106个月的抗逆转录病毒治疗，包括使用一种蛋白酶抑制剂103个月。测量使用重组构建体的表型测定法测量对5种蛋白酶抑制剂的敏感性降低的频率和幅度。敏感性降低定义为与药物敏感对照病毒相比，50%抑制浓度（IC 50）增加> 2.5倍。结果在研究开始时，患者正在接受奈非那韦（63%）、茚地那韦（25%）或其他蛋白酶抑制剂（11%）治疗。这些患者的HIV分离株对所有5种蛋白酶抑制剂均敏感（倍数变化< 2.5），18%的患者对所有5种蛋白酶抑制剂均不敏感（倍数变化< 2.5），8%的患者对任何蛋白酶抑制剂均不敏感。与茚地那韦（P < 0.001）或其他三种药物之一（P <0.001）相比，接受奈非那韦治疗患者的分离株对其他蛋白酶抑制剂的敏感性降低的可能性更小，即使在调整了先前使用蛋白酶抑制剂的持续时间后。观察到对沙奎那韦和安普那韦敏感性降低的频率显著低于其他蛋白酶抑制剂。结论蛋白酶抑制剂交叉耐药的频率和敏感性变化的幅度根据失败的治疗方案中使用的初始蛋白酶抑制剂而变化。与接受其他蛋白酶抑制剂治疗的患者相比，来自奈非那韦治疗失败患者的分离株蛋白酶抑制剂交叉耐药性显著降低。
ObjectiveTo characterize the pattern of HIV-1 susceptibility to protease inhibitors in patients failing an initial protease inhibitor-containing regimen. DesignA cross-sectional analysis of antiretroviral susceptibility. SettingHIV clinics in six metropolitan areas. PatientsEighty-eight HIV-infected adults with HIV RNA > 400 copies/ml after ⩾ 6 months of antiretroviral therapy, including the use of one protease inhibitor for ⩾ 3 months. MeasurementsThe frequency and magnitude of decreased susceptibility, measured with a phenotypic assay using recombinant constructs, to five protease inhibitors. Decreased susceptibility was defined as > 2.5-fold increase in the 50% inhibitory concentration (IC50) compared with drug sensitive control virus. ResultsAt study entry, patients were being treated with nelfinavir (63%), indinavir (25%), or another protease inhibitor (11%). HIV isolates from these patients were susceptible (fold change < 2.5) to all five protease inhibitors in 18% of patients and to none in 8%. Isolates from patients receiving nelfinavir were less likely to have reduced susceptibility to other protease inhibitors than isolates from patients treated with indinavir (P < 0.001) or one of the other three agents (P < 0.001), even after adjustment for the duration of prior protease inhibitor use. Reduced susceptibility to saquinavir and amprenavir was observed significantly less frequently than for the other protease inhibitors. ConclusionThe frequency of protease inhibitor cross-resistance and the magnitude of changes in susceptibility varied according to the initial protease inhibitor used in the failing treatment regimen. Significantly less protease inhibitor cross-resistance was demonstrated for isolates from patients failing a nelfinavir-containing regimen compared with those from patients receiving other protease inhibitors.