Peres-da-Silva Allan, Brandão-Mello Carlos Eduardo, Lampe Elisabeth
Laboratório de Hepatites Virais, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
Hospital Universitário Gaffrée e Guinle/UNIRIO, Rio de Janeiro, Brazil.
Antivir Ther. 2017;22(5):447-451. doi: 10.3851/IMP3131. Epub 2017 Jan 13.
The prevalence of natural polymorphisms associated with resistance to NS5B nucleoside/nucleotide (NI) sofosbuvir is distinct in different geographical regions. In Brazil, direct-acting anti-HCV therapy has recently changed with the introduction of interferon (IFN)-free regimens with sofosbuvir; however, the presence of resistant variants on clinical outcomes remains unknown. The aim of this study was to assess the natural polymorphisms associated with resistance to the NS5B NI sofosbuvir in Brazilian HCV-1 isolates and to compare it with that from other geographical regions.
Nucleotide sequencing of the HCV NS5B gene was performed in serum samples of 95 therapy-naive Brazilian patients infected with subtype 1a (n=43) and 1b (n=52). The sequences were analysed along with 1,525 NS5B sequences from North America, Europe and Asia retrieved from public HCV databases.
In Brazilian HCV-1b patients who have never been exposed to a direct-acting anti-HCV drug, the C316N was detected in 15/52 (28.85%) patients, of these, 2 (3.85%) had single C316N variant, while 13 (25%) presented the double L159F-C316N mutant. A lower rate of L159F-C316N variants was detected in North American (n=9/238; 3.78%, P<0.001), European (n=17/281; 6.05%, P<0.001) and Asian (n=2/173; 1.16%, P<0.001) isolates. No sofosbuvir resistance-associated variants (RAVs) were identified in HCV-1a sequences.
Resistant variants to sofosbuvir were found at different frequencies in worldwide HCV-1b sequences but not in HCV-1a sequences. The high frequency of double mutation L159F-C316N observed in Brazilian HCV-1b patients contrast with the lower rate observed in the three continents studied. The association of these findings and the clinical implications awaits further analysis.
与对NS5B核苷/核苷酸（NI）索磷布韦耐药相关的自然多态性在不同地理区域的流行情况各不相同。在巴西，随着含索磷布韦的无干扰素方案的引入，直接抗丙型肝炎病毒（HCV）治疗最近发生了变化；然而，耐药变异体对临床结局的影响仍不清楚。本研究的目的是评估巴西HCV-1分离株中与对NS5B NI索磷布韦耐药相关的自然多态性，并将其与其他地理区域的情况进行比较。
对95例初治的感染1a亚型（n = 43）和1b亚型（n = 52）的巴西患者的血清样本进行HCV NS5B基因的核苷酸测序。将这些序列与从公共HCV数据库中获取的来自北美、欧洲和亚洲的1525条NS5B序列一起进行分析。
在从未接触过直接抗HCV药物的巴西HCV-1b患者中，15/52（28.85%）的患者检测到C316N，其中2例（3.85%）为单一C316N变异体，而13例（25%）为双重L159F-C316N突变体。在北美（n = 9/238；3.78%，P<0.001）、欧洲（n = 17/281；6.05%，P<0.001）和亚洲（n = 2/173；1.16%，P<0.001）的分离株中检测到的L159F-C316N变异体发生率较低。在HCV-1a序列中未鉴定出与索磷布韦耐药相关的变异体（RAV）。
在全球范围内，HCV-1b序列中发现索磷布韦耐药变异体的频率不同，但在HCV-1a序列中未发现。在巴西HCV-1b患者中观察到的双重突变L159F-C316N的高频率与在研究的三大洲中观察到的较低频率形成对比。这些发现的关联及其临床意义有待进一步分析。
