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阿根廷对HIV整合酶链转移抑制剂的耐药性:首次中期调查

Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey.

作者信息

Cecchini D M, Castillo S, Copertari G, Lacal V, Rodriguez C G, Cassetti I

机构信息

Diego M. Cecchini, Helios Salud SA. Peru 1511/15, Buenos Aires, C1141ACG, Argentina.

出版信息

Rev Esp Quimioter. 2019 Jun;32(3):263-267. Epub 2019 Apr 29.

Abstract

OBJECTIVE

No data on resistance to HIV integrase strand transfer inhibitors (InSTIs) in Argentina are available as access to these drugs and to integrase genotypic resistance test is limited. We aimed to evaluate the clinical profile of patients who underwent an integrase genotypic resistance test, prevalence of InSTI resistance mutations and predicted efficacy of raltegravir, elvitegravir and dolutegravir in our country.

METHODS

Retrospective multicentric pilot survey from January 2011 to November 2017 of InSTI-failing patients assisted at two private and one public healthcare institutions located in Buenos Aires city, Argentina.

RESULTS

Sixty seven patients were included. Patients had a median of 5 (4-7) prior treatments. All patients had InSTI-containing regimens (median exposure of 22.5 months); 94% were under raltegravir therapy and 71.9% had InSTI-resistance mutations. Predominant major mutations were N155H (35.1%), Q148H/R (15.8%) and G140A/S (14%). Considering Stanford HIVdb program, extremely low and identical activity of raltegravir and elvitegravir was described while dolutegravir remained either partially or fully active in 97.7% of patients.

CONCLUSIONS

Integrase resistance test was prescribed almost exclusively in heavily pretrated raltegravir-exposed patients. The three main mutational pathways were described, with a predominance of N155H. Despite almost null susceptibility and extensive cross resistance was shown among raltegravir and elvitegravir, dolutegravir remains active in the majority of patients.

摘要

目的

由于阿根廷获取这些药物及整合酶基因型耐药性检测的机会有限,目前尚无该国关于HIV整合酶链转移抑制剂(InSTIs)耐药性的数据。我们旨在评估接受整合酶基因型耐药性检测的患者的临床特征、InSTI耐药性突变的患病率以及我国raltegravir、elvitegravir和dolutegravir的预测疗效。

方法

对2011年1月至2017年11月期间在阿根廷布宜诺斯艾利斯市的两家私立和一家公立医疗机构接受治疗且InSTIs治疗失败的患者进行回顾性多中心试点调查。

结果

纳入67例患者。患者既往治疗的中位数为5(4 - 7)次。所有患者均接受含InSTIs的治疗方案(中位暴露时间为22.5个月);94%接受raltegravir治疗,71.9%有InSTI耐药性突变。主要的主要突变是N155H(35.1%)、Q148H/R(15.8%)和G140A/S(14%)。根据斯坦福HIV数据库程序,raltegravir和elvitegravir的活性极低且相同,而dolutegravir在97.7%的患者中仍部分或完全保持活性。

结论

整合酶耐药性检测几乎仅在接受过大量raltegravir治疗的患者中进行。描述了三种主要的突变途径,以N155H为主。尽管raltegravir和elvitegravir之间显示出几乎无敏感性和广泛的交叉耐药性,但dolutegravir在大多数患者中仍保持活性。

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