Zhang Jing, Kang Dianmin, Lin Bin, Sun Xiaoguang, Fu Jihua, Bi Zhenqiang, Nkengasong John N, Yang Chunfu
Institute of AIDS/HIV Control and Prevention , Shandong Center for Disease Control and Prevention, Shandong, China.
AIDS Res Hum Retroviruses. 2012 Dec;28(12):1658-65. doi: 10.1089/aid.2012.0019. Epub 2012 Jun 11.
Shandong province has been providing antiretroviral therapy (ART) to eligible HIV/AIDS patients since 2003 using first-line regimens. We conducted a cross-sectional study to assess virological response and resistance development from ART patients. Between 2006 and 2008, blood was collected from 143 ART patients. Viral load (VL) was determined with a detection limit of 50 copies/ml; those with detectable VL were genotyped with dried plasma spots using a broadly sensitive genotyping assay. Resistance mutations were identified using the Stanford HIV drug resistance database. Of the 143 patients, 72% [95% confidence interval (CI): 65.9-78.2] suppressed their VL to <50 copies/ml. Genotyping analysis of the remaining 40 patients revealed that 21 (53%, CI: 37.0-68.0) harbored one or more mutations. The most common mutations were thymidine-analog mutations (22.5%) and M184V (10%) to nucleoside reverse transcriptase inhibitors (NRTIs), and V106I/A /M (17.5%), Y181C (15%), and H221Y (12.5%) to non-NRTIs (NNRTIs); 13 patients had mutations to both NRTIs and NNRTIs. Patients with VL >1000 copies/ml appear to harbor more mutations than those with VL between 50 and 1000 (62.1% vs. 27.3%, p>0.05). Resistance mutations were intensified among 10 patients for whom two sequential specimens were obtained and accumulation of resistance mutations predicted compromised treatment outcomes and future drug selections. This study provides a snapshot of the virological responses and resistance profiles for patients on first-line regimens, indicating that patient monitoring is a critical component in preventing the accumulation of resistance mutations among patients failing their regimens and thus maintaining the effectiveness of the first-line regimens.
自2003年起,山东省就开始使用一线治疗方案为符合条件的艾滋病毒/艾滋病患者提供抗逆转录病毒疗法(ART)。我们开展了一项横断面研究,以评估接受抗逆转录病毒治疗患者的病毒学反应和耐药性发展情况。在2006年至2008年期间,我们收集了143例接受抗逆转录病毒治疗患者的血液样本。使用检测限为50拷贝/毫升的方法测定病毒载量(VL);对于病毒载量可检测到的患者,使用具有广泛敏感性的基因分型检测方法对干血斑进行基因分型。使用斯坦福艾滋病毒耐药数据库识别耐药突变。在这143例患者中,72%[95%置信区间(CI):65.9 - 78.2]的患者将病毒载量抑制到了<50拷贝/毫升。对其余40例患者的基因分型分析显示,21例(53%,CI:37.0 - 68.0)携带一种或多种突变。最常见的突变是针对核苷类逆转录酶抑制剂(NRTIs)的胸苷类似物突变(22.5%)和M184V(10%),以及针对非核苷类逆转录酶抑制剂(NNRTIs)的V106I/A /M(17.5%)、Y181C(15%)和H221Y(12.5%);13例患者同时存在针对NRTIs和NNRTIs的突变。病毒载量>1000拷贝/毫升的患者似乎比病毒载量在50至1000之间的患者携带更多突变(62.1%对27.3%,p>0.05)。在10例获取了连续两份样本的患者中,耐药突变有所增加,耐药突变的积累预示着治疗效果受损以及未来药物选择受限。这项研究提供了接受一线治疗方案患者的病毒学反应和耐药谱的概况,表明患者监测是防止治疗方案失败患者中耐药突变积累从而维持一线治疗方案有效性的关键组成部分。