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接受齐多夫定-拉米夫定联合治疗的患者对齐多夫定和拉米夫定的双重耐药性:与治疗失败的关联

Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapy failure.

作者信息

Miller V, Phillips A, Rottmann C, Staszewski S, Pauwels R, Hertogs K, de Béthune M P, Kemp S D, Bloor S, Harrigan P R, Larder B A

机构信息

Zentrum der Inneren Medizin, Klinikum der J.W. Goethe-Universität, Frankfurt, Germany.

出版信息

J Infect Dis. 1998 Jun;177(6):1521-32. doi: 10.1086/515304.

DOI:10.1086/515304
PMID:9607829
Abstract

Human immunodeficiency virus type 1 (HIV-1) strains dually resistant to zidovudine and lamivudine (3TC) may arise during zidovudine-3TC combination therapy. The objective of this cross-sectional study (n = 43 patients) was to test the association between therapy response (clinical and immunologic) to zidovudine-3TC and the level of phenotypic zidovudine resistance and zidovudine resistance-associated genotype of 3TC-resistant isolates. Other variables included were baseline CD4+ cell count, baseline Centers for Disease Control and Prevention (CDC) classification, virus load, and time receiving zidovudine. Phenotypic resistance was assessed using a recombinant virus assay. Genotypic analysis was based on population sequencing of plasma HIV-1. In a univariate analysis using a logistic regression model, it was found that therapy response was significantly associated with phenotypic and genotypic zidovudine resistance, baseline CD4+ cell count, and virus load. After adjustment for all variables, phenotypic resistance to zidovudine remained the only significantly associated factor, independent of baseline CD4+ cell count, baseline CDC classification, and virus load.

摘要

在齐多夫定与拉米夫定(3TC)联合治疗期间,可能会出现对齐多夫定和拉米夫定双重耐药的1型人类免疫缺陷病毒(HIV-1)毒株。这项横断面研究(n = 43例患者)的目的是检测齐多夫定-3TC治疗反应(临床和免疫方面)与3TC耐药分离株的齐多夫定表型耐药水平及齐多夫定耐药相关基因型之间的关联。其他纳入的变量包括基线CD4+细胞计数、基线疾病控制与预防中心(CDC)分类、病毒载量以及接受齐多夫定治疗的时间。使用重组病毒试验评估表型耐药性。基因分型分析基于血浆HIV-1的群体测序。在使用逻辑回归模型的单变量分析中,发现治疗反应与齐多夫定的表型和基因型耐药、基线CD4+细胞计数以及病毒载量显著相关。在对所有变量进行校正后,齐多夫定的表型耐药仍然是唯一显著相关的因素,独立于基线CD4+细胞计数、基线CDC分类和病毒载量。

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