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乌干达女性单剂量奈韦拉平预防用药7天与6 - 8周后奈韦拉平(NVP)耐药性比较:HIVNET 012研究

Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012.

作者信息

Eshleman S H, Guay L A, Mwatha A, Cunningham S P, Brown E R, Musoke P, Mmiro F, Jackson J B

机构信息

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

出版信息

AIDS Res Hum Retroviruses. 2004 Jun;20(6):595-9. doi: 10.1089/0889222041217518.

Abstract

We compared nevirapine (NVP) resistance (NVPR) mutations in maternal plasma 7 days vs. 6-8 weeks after single-dose NVP prophylaxis. In the HIVNET 012 trial, Ugandan women received a single dose of NVP in labor for prevention of HIV-1 mother-to-child transmission. NVPR mutations were detected in 70 (25%) of 279 women 6-8 weeks after NVP. Samples collected 7 days after NVP were analyzed from a subset of those 279 women. Genotyping was performed with the ViroSeq HIV-1 Genotyping System. NVPR was analyzed using paired samples from 7 days and 6-8 weeks after NVP. Sixty-five women had genotyping results obtained for samples collected at both 7 days and 6-8 weeks post-NVP. Twenty-one (32%) of those women had NVPR mutations detected in one or both samples. This included three women with NVPR at 7 days only, seven with NVPR at 6-8 weeks only, and 11 with NVPR at both time points. Eight women had >1 NVPR mutation detected 7 days after NVP. Y181C was the most common NVPR mutation detected at 7 days, whereas K103N was the most common NVPR mutation detected at 6-8 weeks. We conclude that NVPR may be detected in women as early as 7 days after single-dose NVP. Complex patterns of NVPR are detected in some women. The Y181C NVPR mutation often fades from detection by 6-8 weeks. In contrast, the K103N mutation emerges more slowly, but often remains detectable 6-8 weeks after NVP.

摘要

我们比较了单剂量奈韦拉平(NVP)预防用药7天后与6 - 8周后产妇血浆中奈韦拉平耐药(NVPR)突变情况。在HIVNET 012试验中,乌干达女性在分娩时接受单剂量NVP以预防HIV - 1母婴传播。NVP用药6 - 8周后,在279名女性中的70名(25%)检测到NVPR突变。从这279名女性的一个子集中分析了NVP用药7天后采集的样本。使用ViroSeq HIV - 1基因分型系统进行基因分型。利用NVP用药7天和6 - 8周后的配对样本分析NVPR。65名女性在NVP用药后7天和6 - 8周采集的样本均获得了基因分型结果。其中21名(32%)女性在一个或两个样本中检测到NVPR突变。这包括3名仅在7天检测到NVPR突变的女性、7名仅在6 - 8周检测到NVPR突变的女性以及11名在两个时间点均检测到NVPR突变的女性。8名女性在NVP用药7天后检测到>1个NVPR突变。Y181C是7天检测到的最常见NVPR突变,而K103N是6 - 8周检测到的最常见NVPR突变。我们得出结论,单剂量NVP用药后7天即可在女性中检测到NVPR。在一些女性中检测到复杂的NVPR模式。Y181C NVPR突变通常在6 - 8周时从检测中消失。相比之下,K103N突变出现得更慢,但在NVP用药6 - 8周后通常仍可检测到。

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