Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART
Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART
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DOI：
10.1001/jama.293.7.817
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发表时间：
2005-02-16
影响因子：
120.7
通讯作者：
Siliciano, RF
中科院分区：
文献类型：
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作者：
Nettles, RE;Kieffer, TL;Siliciano, RF
背景许多感染人类免疫缺陷病毒1型（HIV-1）并接受高效抗逆转录病毒治疗的患者会出现间歇性可检测的病毒血症（“blips”），这可能会引起对耐药性的担忧，导致昂贵的病毒RNA重复测量，目的验证信号点代表平均稳态周围随机生物学和统计学变化的假设，在2003年6月19日至2004年2月9日期间，对接受治疗的患者进行密集采样，在3至4个月内（每2-3天一次），以确定脉冲的频率、幅度和持续时间及其与药物水平和其他临床变量的关联。光点定义为HIV-1 RNA测量值大于或等于50拷贝/mL，之前和之后的测量值小于50拷贝/mL，治疗未发生变化。为了确定斑点是否由耐药性引起或导致耐药性，使用超灵敏的基因分型测定来检测斑点之前、期间和之后的耐药性突变。患者是10名HIV-1感染的无症状成年人，由临床医生招募，并在约翰霍普金斯医院的摩尔诊所进行随访。患者的病毒血症抑制到低于50拷贝/mL，同时接受稳定的抗逆转录病毒治疗6个月或更长时间。主要结果Measures在每个时间点，血浆HIV-1 RNA水平测定在2个独立的实验室和耐药突变进行了分析，通过克隆测序。统计分析与平均病毒载量低于50拷贝/mL时的随机试验变异一致。在独立测试中，光点不一致，持续时间短（中位数，
Context Many patients infected with human immunodeficiency virus type 1 (HIV-1) and receiving highly active antiretroviral therapy experience intermittent episodes of detectable viremia ("blips"), which may raise concerns about drug resistance, lead to costly repeat measurements of viral RNA, and sometimes trigger alterations in therapy.Objective To test the hypothesis that blips represent random biological and statistical variation around mean steady-state HIV-1 RNA levels slightly below 50 copies/mL rather than biologically significant elevations in viremia.Design, Setting, and Patients Between June 19, 2003, and February 9, 2004, patients receiving therapy underwent intensive sampling (every 2-3 days) over 3 to 4 months to define the frequency, magnitude, and duration of blips and their association with drug levels and other clinical variables. Blips were defined as HIV-1 RNA measurements greater than or equal to 50 copies/mL preceded and followed by measurements less than 50 copies/mL without a change in treatment. To-determine whether blips result from or lead to drug resistance, an ultrasensitive genotyping assay was used to detect drug resistance mutations before, during, and after blips. Patients were 10 HIV-1-infected asymptomatic adults recruited by clinicians and followed up in the Moore Clinic at the Johns Hopkins Hospital. Patients had suppression of viremia to below 50 copies/mL while receiving a stable antiretroviral regimen for 6 months or longer.Main Outcome Measures At each time point, plasma HIV-1 RNA levels were measured in 2 independent laboratories and drug resistance mutations were analyzed by clonal sequencing.Results With the intensive sampling, blips were detected in 9 of 10 patients. Statistical analysis was consistent with random assay variation around a mean viral load below 50 copies/mL. Blips were not concordant on independent testing and had a short duration (median,