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接受治疗患者中HIV-1耐药性的流行情况:一项法国全国性研究。

Prevalence of HIV-1 drug resistance in treated patients: a French nationwide study.

作者信息

Costagliola Dominique, Descamps Diane, Assoumou Lambert, Morand-Joubert Laurence, Marcelin Anne-Geneviève, Brodard Véronique, Delaugerre Constance, Mackiewicz Vincent, Ruffault Annick, Izopet Jacques, Plantier Jean-Christophe, Tamalet Catherine, Yerly Sabine, Saidi Souhaha, Brun-Vezinet Françoise, Masquelier Bernard

机构信息

INSERM, Unité Mixte de Recherche (UMR) S 720, Université Pierre et Marie Curie-Paris 6, Paris, France.

出版信息

J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):12-8. doi: 10.1097/QAI.0b013e318074eb73.

Abstract

BACKGROUND

Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion of patients for whom new drugs are needed.

METHODS

Patients were consecutively included in 28 centers in France and 1 center in Switzerland if they had a viral load measurement performed in June 2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and gp41 genes were sequenced, and resistance mutations were reported as listed on the Web site ( www.iasusa.org). The genotypic resistance results were interpreted by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) and Stanford algorithms.

RESULTS

The 498 patients included had been exposed to 9 (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4 protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and 83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2, and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The most important differences between algorithms were for PIs. Using the ANRS algorithm and extrapolation on the whole French database, 19% of all treated patients could contribute to the spread of resistance and 4% had complete resistance to 2 classes of antiretroviral drugs.

CONCLUSIONS

The observed patterns of resistance are linked to a long-lasting history of antiretroviral therapy. The frequency of multiresistance can vary according to the interpretation systems.

摘要

背景

从耐药性传播的公共卫生角度以及评估需要新药治疗的患者比例来看,监测接受抗逆转录病毒治疗的患者的HIV-1耐药性很重要。

方法

2004年6月进行病毒载量检测且结果≥1000拷贝/毫升的患者被连续纳入法国的28个中心和瑞士的1个中心。对逆转录酶、蛋白酶和gp41基因进行测序,并按照网站(www.iasusa.org)上列出的内容报告耐药突变。基因型耐药结果由法国国家艾滋病和病毒性肝炎研究机构(ANRS)和斯坦福算法进行解读。

结果

纳入的498例患者曾接触过9种(四分位间距[IQR]:6至12种)抗逆转录病毒药物。患者的病毒携带4种核苷类逆转录酶抑制剂(IQR:1至6种)和4种蛋白酶抑制剂(PI;IQR:2至8种)耐药突变,而44%的患者至少有1种非核苷类逆转录酶抑制剂耐药突变。使用ANRS算法时对至少1种药物耐药的频率为88%,使用斯坦福算法时为83%。使用ANRS算法时对1类、2类和3类药物完全耐药的频率分别为37%、15%和4%,使用斯坦福算法时分别为27%、23%和24%。算法之间最重要的差异在于蛋白酶抑制剂。使用ANRS算法并外推至整个法国数据库,所有接受治疗的患者中有19%可能导致耐药性传播,4%对2类抗逆转录病毒药物完全耐药。

结论

观察到的耐药模式与长期的抗逆转录病毒治疗史有关。多重耐药的频率可能因解读系统而异。

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