Masquelier B, Pellegrin I, Ruffault A, Ragnaud J M, Morlat P, Michelet C, Doignon F, Biteau N, Fleury H J
Laboratoire de Virologie, Université de Bordeaux II, France.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 1;8(4):330-4.
The existence of zidovudine (ZDV)-resistant and didanosine (ddI)-resistant human immunodeficiency-1 (HIV-1) variants mutated in the reverse transcriptase (RT) gene has been previously demonstrated. In this study, we tried to follow up the genotypic changes in the RT after the switch of therapy from ZDV to ddI. We studied HIV-1 isolates from 11 patients undergoing ddI therapy. Genotypic data were obtained with differential polymerase chain reaction (PCR) and with direct sequencing after PCR. The prevalence of ZDV resistance-related mutations showed a very slow decrease, particularly when patients had been treated with ZDV for a long time. The appearance of a mutation at codon 74 seemed to be independent of the presence or absence of ZDV resistance-related mutations. The broad genotypic heterogeneity of the isolates and the complexity of the evolution in one patient's isolates plead for large sequencing studies of the RT genome in new therapeutic approaches.
齐多夫定（ZDV）耐药和去羟肌苷（ddI）耐药的人类免疫缺陷病毒1型（HIV-1）变异体在逆转录酶（RT）基因中发生突变的情况此前已得到证实。在本研究中，我们试图追踪治疗从ZDV转换为ddI后RT基因的基因型变化。我们研究了11例接受ddI治疗患者的HIV-1分离株。通过差异聚合酶链反应（PCR）和PCR后直接测序获得基因型数据。ZDV耐药相关突变的发生率下降非常缓慢，尤其是当患者长期接受ZDV治疗时。密码子74处突变的出现似乎与ZDV耐药相关突变的存在与否无关。分离株广泛的基因型异质性以及一名患者分离株进化的复杂性表明，在新的治疗方法中需要对RT基因组进行大规模测序研究。
