Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated

Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated
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DOI:
10.1086/430741
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发表时间:
2005-07-01
影响因子:
6.4
通讯作者:
Heneine, W
Heneine, W
中科院分区:
医学2区
文献类型:
--
作者:
Johnson, JA;Li, JF;Heneine, W

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传统的序列分析检测到大约40%的妇女在分娩期间接受单剂量奈韦拉平(SD-NVP)后不久就会检测到人类免疫缺陷病毒(HIV)-1耐药性突变。采用灵敏的实时定量聚合酶链式反应方法检测50例感染HIV-1 C亚型的南非妇女在SD-NVP前后的K103N和Y181C耐药突变,通过序列分析,40名妇女没有检测到耐药突变,另有6名妇女在SD-NVP后Y181C阴性。在产后6-36周,40例孕妇中有16例(40%)检出K103N,46例中有5例(11%)检出Y181C。克隆测序证实5个代表性样本中有5个样本为K103N,4个样本中4个样本为Y181C。在新发现的5名患有Y181C的女性中,有4名也患有K103N。这些发现表明,至少65%的女性在接受SD-NVP治疗后出现了耐药性突变,并强调了进一步研究以确定其临床意义的重要性。
Conventional sequence analysis detects human immunodeficiency virus (HIV)-1 drug resistance mutations in similar to 40% of women shortly after they receive intrapartum single-dose nevirapine (SD-NVP). Using sensitive real-time polymerase chain reaction assays for the K103N and Y181C resistance mutations, we tested genotyped virus before and after SD-NVP in 50 South African women infected with HIV-1 subtype C. By sequence analysis, 40 women had no detectable resistance mutations, and an additional 6 women were negative for Y181C after SD-NVP. We found K103N in 16 (40%) of 40 women and Y181C in 5 (11%) of 46 women at 6-36 weeks postpartum. Clonal sequencing confirmed K103N in 5 of 5 representative samples and Y181C in 4 of 4 samples. Four of the 5 women with newly identified Y181C also had K103N. These findings indicate that resistance mutations emerged in at least 65% of the women after SD-NVP and emphasize the importance of further research to determine the clinical implications.