Laboratorio de Medicina Molecular, Hospital Clínico Universidad de Chile, Santiago, Chile.
Centro de Biotecnología Acuícola, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
J Clin Virol. 2014 Jul;60(3):290-4. doi: 10.1016/j.jcv.2014.04.004. Epub 2014 Apr 15.
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.
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.
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%.
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 268,000copies/mL, and 223cells/μL respectively. For X4 samples the values were 368,000copies/mL and 214cells/μL [P>0.05]). Only, 53 patients (12%) could not be analyzed and were categorized as non-reportable.
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.
抗逆转录病毒疗法(ART)可抑制病毒复制。然而,ART 有产生选择性耐药和不良反应的缺点。辅助受体拮抗剂是一组抗逆转录病毒药物,在患者 HIV 嗜性的先验知识下使用。
这项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 变异体的流行率,并研究研究人群中血浆病毒载量(pVL)和 CD4 细胞计数等变量。
从 454 例连续患者中提取 HIV RNA 或前病毒 DNA,并使用 Geno2pheno 进行的基因分型方法进行嗜性检测,设定 FPR 为 5.75%的截止值。
在分析的 454 个人中,299 人(66%)仅携带 R5 变异体。与携带 X4 株的个体(22%)相比,他们的临床特征没有更好。对于 R5 患者,pVL 和 CD4 细胞计数的中位数分别为 268,000 拷贝/mL 和 223 个细胞/μL。对于 X4 样本,这些值分别为 368,000 拷贝/mL 和 214 个细胞/μL [P>0.05])。只有 53 名患者(12%)无法进行分析,并归类为不可报告。
尽管患者接受了多年的治疗,但基因分型方法证实 R5 株更为普遍。与表型测定相比,基因策略被证明是一种更快且具有成本效益的选择。根据我们的结果,每三名接受抗逆转录病毒治疗和病毒学失败的患者中有两名携带 R5 株,可能是使用 CCR5 拮抗剂的候选者。