Kieffer Tara L, Finucane Mariel M, Nettles Richard E, Quinn Thomas C, Broman Karl W, Ray Stuart C, Persaud Deborah, Siliciano Robert F
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21025, USA.
J Infect Dis. 2004 Apr 15;189(8):1452-65. doi: 10.1086/382488. Epub 2004 Apr 5.
Human immunodeficiency virus (HIV) production continues in patients receiving highly active antiretroviral therapy (HAART) with undetectable (<50 copies/mL) virus loads. Our initial cross-sectional study showed that this viremia is composed of viruses that lack new resistance mutations to the HAART regimen. Here we describe a longitudinal, clonal genotypic analysis of plasma virus loads in treated adults who had undetectable virus loads. We document a continuous production of virus in 8 HIV-1-infected adults who maintained suppression of viremia for up to 15 months. Using analytical approaches for distinguishing selected resistance mutations from nonselected mutations and polymerase chain reaction errors, we detected no evolution of resistance in the reverse-transcriptase and protease genes. Sporadic resistance mutations were detected in some viral clones that were not selected for subsequently. Thus, in some patients, HAART suppresses replication to a level that does not allow the evolution of drug resistance over a time frame of years.
在接受高效抗逆转录病毒疗法（HAART）且病毒载量检测不到（<50拷贝/毫升）的患者中，人类免疫缺陷病毒（HIV）仍在持续产生。我们最初的横断面研究表明，这种病毒血症是由对HAART方案缺乏新的耐药突变的病毒组成的。在此，我们描述了对病毒载量检测不到的接受治疗的成年人血浆病毒载量进行的纵向克隆基因型分析。我们记录了8名HIV-1感染成年人中病毒的持续产生情况，这些成年人的病毒血症抑制状态维持了长达15个月。使用区分选定耐药突变与非选定突变以及聚合酶链反应错误的分析方法，我们在逆转录酶和蛋白酶基因中未检测到耐药性的演变。在一些后续未被选择的病毒克隆中检测到了零星的耐药突变。因此，在一些患者中，HAART将病毒复制抑制到了一个在数年时间内不会产生耐药性演变的水平。
