Sui Hongshuai, Gui Tao, Jia Lei, Guo Wei, Han Jingwan, Liu Yongjian, Bao Zuoyi, Li Hanping, Li Jingyun, Li Lin
Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Clinical Laboratory of Beidaihe 281 hospital, Qinhuangdao, Hebei province, China.
Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
PLoS One. 2014 Mar 24;9(3):e91803. doi: 10.1371/journal.pone.0091803. eCollection 2014.
The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05). Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05). All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.
艾滋病毒耐药性的迅速传播正威胁着中国免费高效抗逆转录病毒治疗(HAART)的整体成效。关于耐药性突变已开展了大量工作,然而,其中大部分是基于B亚型。由于不同的基因背景,亚型差异会对耐药性突变的发生产生影响,越来越多的研究已证实了这一点。在中国,主要的流行亚型为CRF07_BC、CRF08_BC、泰国B和CRF01_AE。描述这些亚型中的耐药性突变将有助于为中国人选择治疗方案。在本研究中,比较了中国流行的B亚型、CRF01_AE、CRF07_BC和CRF08_BC毒株中与艾滋病毒耐药性相关位点的氨基酸分布差异。还比较了分别从未经治疗和接受治疗的个体中获得的不同亚型序列的氨基酸组成。B亚型、CRF01_AE和CRF08_BC在耐药组中RT区19个位点的氨基酸比例有显著差异(卡方检验,p<0.05)。遗传屏障分析显示,各亚型之间69、138、181、215和238位点存在显著差异(Kruskal Wallis检验,p<0.05)。所有亚型共有三个最常见的耐药位点103、181和184。在几乎所有未经治疗的患者亚型中,蛋白酶中的许多耐药位点比例惊人地高。这是中国首次针对不同亚型耐药性不同发展情况的全面研究。详细数据将为中国艾滋病毒治疗方案的设计奠定基础,并改善艾滋病毒治疗。