Prevalence of WHO transmitted drug resistance mutations by deep sequencing in antiretroviral-naïve subjects in Hunan Province, China.
Prevalence of WHO transmitted drug resistance mutations by deep sequencing in antiretroviral-naïve subjects in Hunan Province, China.
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DOI：
10.1371/journal.pone.0098740
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kozal MJ
中科院分区：
文献类型：
--
作者：
Xiaobai Z;Xi C;Tian H;Williams AB;Wang H;He J;Zhen J;Chiarella J;Blake LA;Turenchalk G;Kozal MJ
关于世卫组织传播的耐药突变（tdr）在中国湖南省的流行情况的数据很少，这些耐药突变可能影响对一线抗逆转录病毒治疗（ART）的治疗反应。采用深度测序法测定湖南省ART-naïve受试者中WHO NRTI/NNRTI/PI tdr的流行情况。ART-naïve 2010-2011年间在湖南诊断的受试者通过深度测序对具有WHO tdr至1%水平的低频HIV变异进行评估。使用HIVdb.stanford.edu算法对突变进行评分，以推断药物敏感性。对90名ART-naïve受试者的样本进行深度测序；AE亚型占83.3%。所有受试者均为晚期疾病（平均CD4计数134细胞/mm3）。深度测序结果显示，25.6%（23/90）的受试者携带主要WHO NRTI/NNRTI tdr，变异频率水平≥1%；16.7%（15/90）有NRTI TDR， 12.2%（11/90）有重度NNRTI TDR。大多数NRTI/NNRTI突变在变异水平<5%时被发现。通过HIVdb.stanford.edu对突变进行分析，7.8%的受试者变异具有高水平的奈韦拉平耐药性；4.4%的患者有高水平的NRTI抗性。深度测序鉴定出24名（27.6%）受试者具有PI TDR或hivdb.stanford.edu PI突变（算法值≥15）的变体。17例（19.5%）患者的PI tdr水平为bb10 ~ 1%。ART-naïve来自中国湖南省的主要感染AE亚型的受试者通过深度测序经常具有具有WHO NRTI/NNRTI tdr的HIV变体，这将影响该地区使用的一线抗逆转录病毒治疗。在7.8%的受试者中发现了赋予奈韦拉平高水平耐药的特异性突变。大多数检测到的tdr水平都低于5%，这可能是由于受试者在检测时患有晚期慢性疾病。PI tdr被频繁发现，但发现是孤立的，变异频率低。由于PI/r在湖南的使用频率较低，PI突变的存在可能代表AE亚型在低变异水平频率下的自然多态性。
There are few data on the prevalence of WHO transmitted drug resistance mutations (TDRs) that could affect treatment responses to first line antiretroviral therapy (ART) in Hunan Province, China. Determine the prevalence of WHO NRTI/NNRTI/PI TDRs in ART-naïve subjects in Hunan Province by deep sequencing. ART-naïve subjects diagnosed in Hunan between 2010–2011 were evaluated by deep sequencing for low-frequency HIV variants possessing WHO TDRs to 1% levels. Mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility. Deep sequencing was performed on samples from 90 ART-naïve subjects; 83.3% were AE subtype. All subjects had advanced disease (average CD4 count 134 cells/mm3). Overall 25.6%(23/90) of subjects had HIV with major WHO NRTI/NNRTI TDRs by deep sequencing at a variant frequency level ≥1%; 16.7%(15/90) had NRTI TDR and 12.2%(11/90) had a major NNRTI TDR. The majority of NRTI/NNRTI mutations were identified at variant levels <5%. Mutations were analyzed by HIVdb.stanford.edu and 7.8% of subjects had variants with high-level nevirapine resistance; 4.4% had high-level NRTI resistance. Deep sequencing identified 24(27.6%) subjects with variants possessing either a PI TDR or hivdb.stanford.edu PI mutation (algorithm value≥15). 17(19.5%) had PI TDRs at levels >1%. ART-naïve subjects from Hunan Province China infected predominantly with subtype AE frequently possessed HIV variants with WHO NRTI/NNRTI TDRs by deep sequencing that would affect the first line ART used in the region. Specific mutations conferring nevirapine high-level resistance were identified in 7.8% of subjects. The majority of TDRs detected were at variant levels <5% likely due to subjects having advanced chronic disease at the time of testing. PI TDRs were identified frequently, but were found in isolation and at low variant frequency. As PI/r use is infrequent in Hunan, the existence of PI mutations likely represent AE subtype natural polymorphism at low variant level frequency.