Ma Liying, Huang Jianghong, Xing Hui, Yuan Lin, Yu Xiaoling, Sun Jianping, Huang Yang, Qu Shuiling, Feng Yi, Liao Linjie, Liu Shuwen, Shao Yiming
State Key Laboratory for Infection Disease Prevention and Control, National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing, China.
AIDS Res Hum Retroviruses. 2010 Sep;26(9):1007-13. doi: 10.1089/aid.2009.0252.
The objective of this study was to assess the patterns of genotypic and phenotypic resistance in a population of blood donor patients infected with HIV-1 subtype B' (Thai B', a clade of HIV-1 B) from central China, previously treated and harboring NRTI and NNRTI resistance mutations, with the purpose of designing effective therapeutic regimens. The HIV-1 pol genes from 65 patients were sequenced and estimated for drug resistance while the viruses isolated from the patients were used to analyze the phenotype based on the TZM-bl cell line. All the HIV-1 strains harboring one or more drug resistance mutations to HIV-1 RTIs possessed high cross-resistance to EFV (100%) and DLV (92%), as well as to ABC (84%) and TDF (77%), which are much higher than both FTC and 3TC (42%). There were more thymidine analog mutation (TAM)-associated mutations in the AZT/ddI/NVP group (62.5%) than in the d4T/ddI/NVP group (32.65%). A phenotypic assay showed high concordance between genotypic and phenotypic cross-resistance. This study showed there was a high level of cross-drug resistance to HIV-1 RTIs among Chinese AIDS patients harboring resistant strains, and there is also a high prevalence of primary resistance to 3TC, suggesting that one important recommendation should be the realization of genotypes in all naive patients due to the high prevalence of NRTI and NNRTI mutations.
本研究的目的是评估中国中部地区一群感染HIV-1 B'亚型(泰国B',HIV-1 B的一个分支)的献血患者的基因型和表型耐药模式,这些患者先前接受过治疗且携带核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)耐药突变,旨在设计有效的治疗方案。对65例患者的HIV-1 pol基因进行测序并评估耐药性,同时将从患者中分离出的病毒用于基于TZM-bl细胞系分析表型。所有对HIV-1逆转录酶抑制剂(RTIs)携带一种或多种耐药突变的HIV-1毒株对依非韦伦(EFV,100%)和地拉韦啶(DLV,92%)以及阿巴卡韦(ABC,84%)和替诺福韦(TDF,77%)具有高度交叉耐药性,这远高于恩曲他滨(FTC)和拉米夫定(3TC,42%)。齐多夫定/去羟肌苷/奈韦拉平组(62.5%)中与胸苷类似物突变(TAM)相关的突变比司他夫定/去羟肌苷/奈韦拉平组(32.65%)更多。表型分析显示基因型和表型交叉耐药之间具有高度一致性。本研究表明,在中国携带耐药毒株的艾滋病患者中,对HIV-1 RTIs存在高水平的交叉耐药,并且对3TC的原发耐药率也很高,这表明由于NRTI和NNRTI突变的高流行率,一项重要建议应该是对所有初治患者进行基因型检测。