Liu Li, Lu Hong Zhou, Henry Mireille, Tamalet Catherine
Department of Infectious Disease, Shanghai Public Health Center, Shanghai, People's Republic of China.
J Med Virol. 2007 Oct;79(10):1593-9. doi: 10.1002/jmv.20998.
Few data are available for genotypic patterns within human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) in drug-naive patients and RT inhibitor (RTI) treated patients in China. This study aimed at characterizing the polymorphism of RT HIV-1 in the absence of drug treatment and to identify known and unknown mutations emerging under RTI selective pressure. The HIV-1 RT gene from 21 drug-naive patients and 81 RTI treated patients from three provinces in China was analyzed. Most patients (>80%) received a triple regimen including stavudine (d4T) plus didanosine (ddI) and nevirapine (NVP), or d4T plus lamivudine (3TC) and efavirenz (EFV), or zidovudine (AZT) +ddI + NVP. In untreated patients, four highly polymorphic positions were found (122, 200, 207, and 211). In treated patients, two patterns of resistance associated mutations (RAMs) were observed: (1) K65R (9.8%), L74V (7.4%), M184V (7.4%), Q151M (5%), and thymidine analogue mutations (TAMs) (9.3%) including T215Y (5.5%), in patients who underwent ddI + d4T + NVP. (2) T215Y (23%), M184V (20%), and TAMs (15.4%) in patients receiving d4T + 3TC + EFV. In all cases, a high prevalence of non-nucleoside RTIs (NNRTI) RAMs (41.9%) was found. Four RTI suspected new RAMs were described at position 142, 221, 224, and 228. An association between H221Y and L228H/R with Y181C was noted. These data highlight the predominant spread of NNRTI RAM in China, depict the specific genotypic pattern of RTI selected mutations in China, and suggest the association of newly described mutations with RTI therapy.
在中国，关于初治患者和接受逆转录酶抑制剂（RTI）治疗的患者体内人类免疫缺陷病毒1型（HIV-1）逆转录酶（RT）的基因型模式，可用数据较少。本研究旨在描述未经药物治疗时HIV-1 RT的多态性，并识别在RTI选择压力下出现的已知和未知突变。对来自中国三个省份的21例初治患者和81例接受RTI治疗的患者的HIV-1 RT基因进行了分析。大多数患者（>80%）接受了包含司他夫定（d4T）加去羟肌苷（ddI）和奈韦拉平（NVP），或d4T加拉米夫定（3TC）和依非韦伦（EFV），或齐多夫定（AZT）+ddI+NVP的三联疗法。在未治疗的患者中，发现了四个高度多态性位点（122、200、207和211）。在接受治疗的患者中，观察到两种耐药相关突变（RAM）模式：（1）接受ddI+d4T+NVP治疗的患者中，K65R（9.8%）、L74V（7.4%）、M184V（7.4%）、Q151M（5%）以及包括T215Y（5.5%）在内的胸苷类似物突变（TAM）（9.3%）。（2）接受d4T+3TC+EFV治疗的患者中，T215Y（23%）、M184V（20%）和TAM（15.4%）。在所有病例中，发现非核苷类逆转录酶抑制剂（NNRTI）RAM的高流行率（41.9%）。在第142、221、224和228位描述了四种疑似RTI的新RAM。注意到H221Y和L228H/R与Y181C之间存在关联。这些数据突出了NNRTI RAM在中国的主要传播情况，描绘了中国RTI选择突变的特定基因型模式，并表明新描述的突变与RTI治疗之间的关联。
