C型1型人类免疫缺陷病毒单剂量奈韦拉平治疗后血浆和母乳中的耐药性：群体和克隆序列分析

Drug resistance in plasma and breast milk after single-dose nevirapine in subtype C HIV type 1: population and clonal sequence analysis.

作者信息

Kassaye Seble, Lee Esther, Kantor Rami, Johnston Elizabeth, Winters Mark, Zijenah Lynn, Mateta Patrick, Katzenstein David

机构信息

Department of Medicine and Infectious Diseases, Stanford University, Stanford, California 94305, USA.

出版信息

AIDS Res Hum Retroviruses. 2007 Aug;23(8):1055-61. doi: 10.1089/aid.2007.0045.

DOI:10.1089/aid.2007.0045

PMID:17725424

Abstract

Single-dose nevirapine (SD NVP) reduces intrapartum HIV-1 transmission, but nonnucleoside reverse transcription (NNRTI) resistance mutations can emerge. Population sequencing among 32 subtype C HIV-1-infected, SD NVP-exposed Zimbawean women demonstrated NNRTI resistance in 25/32 (78%) women: 23/30 (77%) at 2 weeks, 11/31 (35%) at 8 weeks, and 5/27 (19%) at 24 weeks. A total of 447 unique TA clones (median = 28 per time point), from four women with resistance at 8 weeks but wild-type virus by population sequence at 24 weeks, identified NNRTI mutations in a median of 76% (range: 55-96%) of individual clones at 2 weeks, 48% (range: 33-80%) at 8 weeks, and 5% (range: 0-15%) by 24 weeks. NNRTI mutations in breast milk clones at 2 and weeks from one woman varied significantly from plasma. Population sequencing underestimates the diversity of NNRTI resistance mutations within minority populations following SD NVP in subtype C HIV-1 viral RNA in plasma and breast milk.

摘要

单剂量奈韦拉平（SD NVP）可降低分娩时HIV-1传播，但可能会出现非核苷类逆转录酶（NNRTI）耐药突变。对32名感染C亚型HIV-1且暴露于SD NVP的津巴布韦女性进行群体测序，结果显示25/32（78%）的女性存在NNRTI耐药：2周时为23/30（77%），8周时为11/31（35%），24周时为5/27（19%）。从4名在8周时出现耐药但在24周时群体测序显示为野生型病毒的女性中，共获得447个独特的TA克隆（每个时间点中位数为28个），结果发现2周时中位数为76%（范围：55 - 96%）的单个克隆存在NNRTI突变，8周时为48%（范围：33 - 80%），到24周时为5%（范围：0 - 15%）。一名女性在2周和8周时母乳克隆中的NNRTI突变与血浆中的差异显著。群体测序低估了C亚型HIV-1血浆和母乳病毒RNA在接受SD NVP后少数群体中NNRTI耐药突变的多样性。