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在资源有限的环境中,评估依曲韦林在基于非核苷类逆转录酶抑制剂的初始治疗方案失败后的二线抗逆转录病毒治疗中的作用。

Evaluating the role of etravirine in the second-line antiretroviral therapy after failing an initial non-nucleoside reverse transcriptase inhibitor-based regimen in a resource-limited setting.

作者信息

Sungkanuparph Somnuek, Manosuthi Weerawat, Kiertiburanakul Sasisopin, Piyavong Bucha, Chantratita Wasun

机构信息

Department of Medicine, Ministry of Public Health, Nonthaburi, Thailand.

出版信息

Curr HIV Res. 2008 Sep;6(5):474-6. doi: 10.2174/157016208785861230.

Abstract

Etravirine demonstrates activity against NNRTI-resistant HIV-1 but its efficacy depends on the number of etravirine resistance-associated mutations (RAMs). This study aimed to evaluate the role of etravirine in the second regimen in a resource-limited setting. Genotype resistance assay was conducted in a cohort of HIV-infected patients who experienced virological failure from an initial NNRTI-based regimen. We focused on etravirine-RAMs previously described: V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and G190A/S. Frequency and predicting factors for <or=2 etravirine-RAMs were evaluated. There were 158 patients with a median duration of ART prior to failure of 22 months. The median CD4 cell count and HIV-1 RNA at the time of virological failure were 173 cells/mm(3) and 4.1 log copies/mL, respectively. Of all, 75.3% of patients were predicted to have <or=2 etravirine-RAMs. From logistic regression, there was no clinical factor to predict etravirine susceptibility. Patients with <or=2 etravirine-RAMs had lower rates of K65R (3.4% vs 17.9%, p=0.005), Q151M (5.9% vs 20.5%, p=0.012), and multi-NRTI resistance mutations (16.8% vs 48.7%, p<0.001) when compared to patients with >2 etravirine-RAMs. Etravirine may have activity for using in the second regimen in most patients in resource-limited setting who fail an initial NNRTI-based regimen. Genotype testing is needed to identify this group. Some of these patients, indicated by genotype results, may be able to use etravirine plus 2 active NRTIs for second ART regimen. This strategy may be an option for patients who cannot afford or tolerate protease inhibitor. Prospective study to evaluate this strategy should be conducted in resource-limited setting.

摘要

依曲韦林对耐非核苷类逆转录酶抑制剂(NNRTI)的HIV-1具有活性,但其疗效取决于与依曲韦林耐药相关的突变(RAMs)数量。本研究旨在评估依曲韦林在资源有限环境下二线治疗方案中的作用。对一组因初始基于NNRTI的治疗方案出现病毒学失败的HIV感染患者进行了基因型耐药检测。我们重点关注先前描述的依曲韦林-RAMs:V90I、A98G、L100I、K101E/P、V106I、V179D/F、Y181C/I/V和G190A/S。评估了依曲韦林-RAMs≤2的频率及预测因素。共有158例患者,失败前抗逆转录病毒治疗(ART)的中位持续时间为22个月。病毒学失败时的中位CD4细胞计数和HIV-1 RNA分别为173个细胞/mm³和4.1 log拷贝/mL。总体而言,75.3%的患者预计依曲韦林-RAMs≤2。经逻辑回归分析,没有临床因素可预测依曲韦林的敏感性。与依曲韦林-RAMs>2的患者相比,依曲韦林-RAMs≤2的患者K65R发生率较低(3.4%对17.9%,p = 0.005)、Q151M发生率较低(5.9%对20.5%,p = 0.012)以及多核苷类逆转录酶抑制剂耐药突变发生率较低(16.8%对~`48.7%,p<0.001)。在资源有限环境下,对于大多数因初始基于NNRTI的治疗方案失败的患者,依曲韦林可能可用于二线治疗方案。需要进行基因型检测以识别这组患者。根据基因型结果显示,其中一些患者可能能够使用依曲韦林加两种活性核苷类逆转录酶抑制剂进行二线ART治疗方案。对于无法负担或耐受蛋白酶抑制剂的患者,该策略可能是一种选择。应在资源有限环境下开展前瞻性研究以评估该策略。

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