Prevalence of R5 and X4 HIV variants in antiretroviral treatment experienced patients with virologic failure

Prevalence of R5 and X4 HIV variants in antiretroviral treatment experienced patients with virologic failure
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DOI:
10.1016/j.jcv.2014.04.004
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发表时间:
2014-07-01
影响因子:
8.8
通讯作者:
Afani, A.
Afani, A.
中科院分区:
医学3区
文献类型:
--
作者:
Ferrer, P.;Tello, M.;Afani, A.

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背景:抗逆转录病毒疗法(ART)抑制病毒复制。然而,ART 的缺点是会产生选择性耐药性和不良事件。共受体拮抗剂是一类抗逆转录病毒药物,在事先了解患者 HIV 趋向性的情况下使用。 目的:本工作的目的是估计接受抗逆转录病毒治疗和病毒学失败的智利患者中 R5 和 X4 变异的患病率,并调查研究人群中血浆病毒载量 (pVL) 和 CD4 细胞计数等变量。 研究设计:从 454 名连续患者中提取 HIV RNA 或前病毒 DNA,并进行趋向性测试使用 Geno2pheno 执行的基因型方法设置 FPR 5.75% 的截止值。结果:在分析的 454 名个体中,299 名 (66%) 只携带 R5 变异。他们没有表现出比携带 X4 菌株的个体(22%)更好的临床特征。对于 R5 患者,pVL 和 CD4 细胞计数的中位数分别为 268,000 个拷贝/mL 和 223 个细胞/pi。对于 X4 样品,值为 368,000 拷贝/mL 和 214 个细胞/pi [A> 0.05])。只有 53 名患者 (12%) 无法进行分析,被归类为不可报告。结论:基因分型方法证实,尽管患者已经接受了多年的治疗,但 R5 菌株更为普遍。与表型测定相比,基因型策略被证明是一种更快、更具成本效益的选择。根据我们的结果,每三名接受抗逆转录病毒治疗且病毒学失败的患者中就有两名携带 R5 毒株,并且可能是使用 CCR5 拮抗剂的候选者。 (C) 2014 Elsevier B.V. 保留所有权利。
Background: Antiretroviral therapy (ART) inhibits virus replication. Nevertheless, ART has the disadvantage of generate selective resistance and adverse events. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV tropism.Objectives: The purpose of this work was to estimate the prevalence of R5 and X4 variants among Chilean patients under antiretroviral therapy and virological failure and investigate variables such as plasma viral load (pVL) and CD4 cell count in the population studied.Study design: HIV RNA or proviral DNA was extracted from 454 consecutives patients and tropism testing was performed using a genotypic method performed with Geno2pheno setting a cutoff value for FPR 5.75%.Results: Among 454 individuals analyzed, 299 (66%) harbouring exclusively R5 variants. They not displayed a better clinical profile than individuals harbouring X4 strains (22%). For R5 patients the median of pVL and CD4 cell count were 268,000 copies/mL, and 223 cells/pi respectively. For X4 samples the values were 368,000 copies/mL and 214 cells/pi [A> 0.05]). Only, 53 patients (12%) could not be analyzed and were categorized as non-reportable.Conclusions: The genotypic method confirmed that R5 strains were more prevalent despite the fact that patients were treatment-experienced for several years. The genotypic strategy proved to be a faster and cost-effective option as compared to phenotypic assays. According to our results, two of every three patients under antiretroviral therapy and with virologic failure harbour R5 strains, and may be candidates for use of a CCR5 antagonist. (C) 2014 Elsevier B.V. All rights reserved.