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与依非韦伦治疗经非核苷类逆转录酶抑制剂治疗的 HIV-1 感染患者的病毒学应答相关的因素。

Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients.

机构信息

Department of Virology, Pitié-Salpêtrière Hospital, 83 Boulevard de l'Hôpital, 75013 Paris, France.

出版信息

Antimicrob Agents Chemother. 2010 Jan;54(1):72-7. doi: 10.1128/AAC.01051-09. Epub 2009 Nov 9.

Abstract

To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log(10) copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm(3) (IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log(10) copies/ml and/or HIV-1 RNA level of <50 copies/ml. No difference in VR was observed between patients receiving or not a boosted PI in combination with ETR. Factors independently associated with a better VR to ETR were the number of drugs (among enfuvirtide, darunavir, or raltegravir) used for the first time in combination with ETR and the presence of the K103N mutation at baseline. Mutations Y181V and E138A were independently associated with poor VR, whereas no effect of the Y181C on VR was observed. In conclusion, ETR was associated with high response rates in NNRTI-experienced patients in combination with other active drugs regardless of the therapeutic class used.

摘要

为了确定与依曲韦林(ETR)为基础的治疗方案的病毒学应答(VR)相关的因素,研究了 243 名先前接受过非核苷类逆转录酶抑制剂(NNRTIs)治疗的患者。研究了基线 HIV-1 RNA、CD4 细胞计数、既往使用的 NNRTIs、57 种 NNRTI 耐药突变、核苷类逆转录酶抑制剂(NRTIs)和蛋白酶抑制剂(PI)的基因型敏感性评分(GSS)、以及首次与 ETR 联合使用的新药数量对 ETR 方案的 VR 的影响。在 243 名患者中,中位基线 HIV-1 RNA 水平为 4.4 log10 拷贝/ml(四分位间距 [IQR],3.7 至 4.9),中位 CD4 计数为 175 个细胞/mm3(IQR,69 至 312)。患者既往暴露于中位数为 6 种 NRTIs、1 种 NNRTI 和 5 种 PI。总体而言,82%的患者在第 2 个月时达到了 VR,定义为 HIV-1 RNA 下降至少 1.5 log10 拷贝/ml 和/或 HIV-1 RNA 水平<50 拷贝/ml。接受或不接受与 ETR 联合使用的增效 PI 的患者在 VR 方面无差异。与 ETR 更好的 VR 相关的独立因素是首次与 ETR 联合使用的药物数量(恩夫韦肽、达芦那韦或拉替拉韦)和基线时 K103N 突变的存在。Y181V 和 E138A 突变与 VR 不良相关,而 Y181C 对 VR 无影响。总之,ETR 与其他活性药物联合应用于 NNRTI 经验丰富的患者中,与治疗类别无关,可获得高反应率。

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