Couto-Fernandez J C, Silva-de-Jesus C, Veloso V G, Rachid M, Gracie R S G, Chequer-Fernandez S L, Oliveira S M, Arakaki-Sanchez D, Chequer P J N, Morgado M G
Laboratório de AIDS e Imunologia Molecular, Departamento de Imunologia, Instituto Oswaldo Cruz-Fiocruz, 21045-900 Rio de Janeiro, RJ, Brazil.
Mem Inst Oswaldo Cruz. 2005 Feb;100(1):73-8. doi: 10.1590/s0074-02762005000100014. Epub 2005 Apr 12.
In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeq Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.
为评估1型人类免疫缺陷病毒（HIV-1）的耐药突变谱，并评估巴西里约热内卢州HIV-1基因亚型的分布情况，于2002年和2003年收集了547例接受抗逆转录病毒（ARV）治疗失败的HIV-1感染患者的血样，送至里约热内卢的Renageno实验室（奥斯瓦尔多·克鲁兹基金会）进行病毒耐药基因分型。使用ViroSeq基因分型系统（美国Celera诊断公司-雅培）进行病毒耐药基因分型。基于聚合酶（pol）基因序列（蛋白酶和逆转录酶-RT区域）的HIV-1基因亚型分析结果如下：B亚型（91.2%）、F亚型（4.9%）以及B/F病毒重组形式（3.3%）。在两名患者中鉴定出C亚型（0.4%），发现一名患者感染重组CRF_02/AG病毒（0.2%）。与逆转录酶抑制剂相关的HIV-1基因分型谱显示，M184V突变频率较高，其次是与胸苷相关的突变。K103N突变是最常见的非核苷类逆转录酶抑制剂耐药突变，与蛋白酶抑制剂相关的耐药性表现为L63P、L10F/R和A71V等次要突变最为常见。在里约热内卢接受HIV-1治疗的患者中观察到很大比例的B亚型。此外，我们还发现了耐药HIV-1 C亚型的传播情况，并首次报告了非洲重组CRF_02/AG病毒在巴西里约热内卢的出现。本研究观察到HIV-1亚型与蛋白酶耐药突变之间存在明显关联。对HIV-1治疗失败患者维持耐药基因分型项目，对于ARV治疗的管理以及尝试和监测巴西HIV-1亚型的流行情况非常重要。
