Rey D, Hughes M, Pi J T, Winters M, Merigan T C, Katzenstein D A
Center for AIDS Research, Stanford University Medical Center, California 94305-5107, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Mar 1;17(3):203-8. doi: 10.1097/00042560-199803010-00003.
Treatment of HIV infection with zidovudine (ZDV) may select for changes in the genetic sequence of the viral reverse transcriptase (RT) that imparts drug resistance. The presence of a 2-bp mutation at codon 215 of RT (from threonine to phenylalanine or tyrosine) was assessed in plasma viral RNA in 85 subjects treated with ZDV in the AIDS Clinical Trials Group (ACTG) 175 virology substudy. Median CD4 cell numbers, HIV plasma RNA levels, and infectious titers of virus were significantly different over 56 weeks of treatment among 58 subjects with the wild-type threonine at codon 215 virus at study entry compared with the 27 subjects with mutations to phenylalanine or tyrosine (MUT) virus. Thirty percent (13 of 44 subjects) with wild-type virus at study entry developed a new codon 215 mutation. Genotypic resistance at codon 215 in plasma HIV RNA is associated with the subsequent immunologic and virologic failure of ZDV monotherapy in subjects with 200 to 500 CD4 cells/mm3.
用齐多夫定（ZDV）治疗HIV感染可能会导致病毒逆转录酶（RT）基因序列发生变化，从而产生耐药性。在艾滋病临床试验组（ACTG）175病毒学子研究中，对85例接受ZDV治疗的受试者血浆病毒RNA中RT第215密码子处2个碱基对的突变（从苏氨酸变为苯丙氨酸或酪氨酸）情况进行了评估。与27例携带第215密码子突变为苯丙氨酸或酪氨酸（MUT）病毒的受试者相比，在研究开始时携带第215密码子野生型苏氨酸病毒的58例受试者在56周的治疗期间，其CD4细胞数中位数、HIV血浆RNA水平和病毒感染滴度存在显著差异。在研究开始时携带野生型病毒的受试者中，有30%（44例中的13例）出现了新的第215密码子突变。血浆HIV RNA中第215密码子的基因型耐药性与CD4细胞计数为200至500个/mm³的受试者接受ZDV单药治疗后随后出现的免疫和病毒学治疗失败相关。
