Efficient Suppression of Minority Drug-Resistant HIV Type 1 (HIV-1) Variants Present at Primary HIV-1 Infection by Ritonavir-Boosted Protease Inhibitor-Containing Antiretroviral Therapy
Efficient Suppression of Minority Drug-Resistant HIV Type 1 (HIV-1) Variants Present at Primary HIV-1 Infection by Ritonavir-Boosted Protease Inhibitor-Containing Antiretroviral Therapy
复制标题
含利托那韦的蛋白酶抑制剂增强型抗逆转录病毒疗法能有效抑制初次感染 HIV-1 时出现的少数耐药 HIV-1 型 (HIV-1) 变异株
DOI：
10.1086/651136
复制
发表时间：
2010-04-01
影响因子：
6.4
通讯作者：
Guenthard, Huldrych F.
中科院分区：
文献类型：
--
作者：
Metzner, Karin J.;Rauch, Pia;Guenthard, Huldrych F.
背景选择耐药人类免疫缺陷病毒1型（HIV-1）的既存少数变异体可能导致接受抗逆转录病毒治疗（ART）的患者的病毒学失败，遗传抗性障碍低。我们研究了ART治疗前几周内少数变体的治疗反应和动态，其中包含一种利托那韦增强的蛋白酶抑制剂（PI）和2种核苷逆转录酶抑制剂（NRTI），这是一种具有高遗传耐药屏障的方案。方法。采用等位基因特异性聚合酶链反应检测了109例原发性HIV感染患者在开始ART前的血浆样本和17例患者在早期ART期间病毒衰减过程中获得的样本中的K103 N和M184 V变异体。在ART之前的109例患者中，有15例（13.8%）检测到K103 N和/或M184 V突变作为少数变异。在ART的第一周内，在15例既存耐药突变的患者中，7例未观察到这些变异体的选择，在10例既存耐药突变的患者中也未观察到任何选择。大多数患者在确诊HIV-1感染后立即接受ART，显示病毒载量迅速下降，并经历了足够的病毒血症抑制，
Background. Selection of preexisting minority variants of drug-resistant human immunodeficiency virus type 1 (HIV-1) can lead to virological failure in patients who receive antiretroviral therapy (ART) with low genetic resistance barriers. We studied treatment response and dynamics of minority variants during the first weeks of ART containing a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs), which is a regimen with a high genetic resistance barrier.Methods. Plasma samples obtained prior to initiation of ART from 109 patients with primary HIV infection and samples obtained during viral decay during early ART from 17 of these 109 patients were tested by allele-specific polymerase chain reaction for K103N and M184V variants.Results. K103N and/or M184V mutations were detected in 15 (13.8%) of 109 patients prior to ART as minority variants. No selection of these variants was observed within the first weeks of ART in 7 of 15 patients with preexisting drug resistance mutations, nor was any selection observed in 10 patients without preexisting drug resistance mutations. Most patients received ART immediately after diagnosis of HIV-1 infection, showed a rapid decrease in viral load, and experienced sufficient suppression of viremia for