Read P, Costelloe S, Mullen J, O'Shea S, Lyons F, Hay P, Welch J, Larbalestier N, Taylor Gp, de Ruiter A
Department of Genitourinary Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
HIV Med. 2008 Aug;9(7):448-51. doi: 10.1111/j.1468-1293.2008.00594.x.
To determine whether mutations conferring drug resistance are detectable after zidovudine monotherapy (ZDVm) in pregnancy, using both standard genotyping and more sensitive cloning assays.
Post-delivery samples from women meeting the British HIV Association guidelines criteria for the use of ZDVm in the prevention of mother-to-child transmission (MTCT) and who received ZDVm were analysed using the Trugene HIV-1 genotyping assay. In order to detect drug-resistant minority species, samples from a sub-group of 14 women were evaluated for minority drug-resistant variants. Nested polymerase chain reaction (PCR) products from the reverse transcriptase (RT) gene (codons 1-258) were cloned into the pCR4 Blunt TOPO cloning vector. Sequences were submitted to the Stanford University HIV Drug Resistance Database for analysis.
Eighty women met the inclusion criteria. Successful genotypes were obtained from 53. There were no new mutations conferring resistance to ZDV detected post-delivery using either standard genotyping or cloning for minority species.
A short course of ZDVm in carefully selected women does not lead to the emergence of drug resistance based on either standard genotyping or cloning for the detection of minority species. Therefore, this strategy can still be considered in women wishing to prevent MTCT while minimizing antiretroviral exposure, without fear of compromising their future HIV care.
采用标准基因分型和更灵敏的克隆分析方法，确定在孕期接受齐多夫定单药治疗（ZDVm）后是否能检测到赋予耐药性的突变。
对符合英国HIV协会关于使用ZDVm预防母婴传播（MTCT）指南标准且接受ZDVm治疗的女性产后样本，使用Trugene HIV-1基因分型检测法进行分析。为检测耐药性少数群体，对14名女性亚组的样本进行了少数群体耐药性变异评估。将来自逆转录酶（RT）基因（密码子1 - 258）的巢式聚合酶链反应（PCR）产物克隆到pCR4 Blunt TOPO克隆载体中。序列提交至斯坦福大学HIV耐药数据库进行分析。
80名女性符合纳入标准。53例获得了成功的基因分型。使用标准基因分型或少数群体克隆检测法，产后均未检测到赋予齐多夫定耐药性的新突变。
在精心挑选的女性中进行短疗程的ZDVm治疗，基于标准基因分型或少数群体克隆检测法，不会导致耐药性的出现。因此，对于希望预防母婴传播同时尽量减少抗逆转录病毒药物暴露的女性，仍可考虑采用该策略，而无需担心会影响其未来的HIV治疗。
