Fox Zoe V, Geretti Anna Maria, Kjaer Jesper, Dragsted Ulrik Bak, Phillips Andrew N, Gerstoft Jan, Staszewski Schlomo, Clotet Bonaventura, von Wyl Viktor, Lundgren Jens D
Copenhagen HIV Programme, Medical Faculty at University of Copenhagen, Denmark.
AIDS. 2007 Oct 1;21(15):2033-42. doi: 10.1097/QAD.0b013e32825a69e4.
: Limited information exists on the prognostic value of genotypic interpretation systems (GISs) for ritonavir-boosted protease inhibitors (PI/rs). We compared PI/r resistance levels ascribed by four GIS and examined their abilities to predict HIV-RNA reductions after starting a PI/r-based regimen (baseline).
: Data on viraemic (HIV-RNA > 500 copies/ml) patients starting a PI/r with a baseline resistance test were combined from an observational cohort study (EuroSIDA) and three randomized trials (MaxCmin1; MaxCmin2 and COLATE). The GIS surveyed were ANRS, DMC, REGA and Stanford. Factors associated with HIV-RNA change were identified through censored regression analysis.
: We included 744 patients, of whom 67% were PI experienced. At baseline 12-28% (depending on the GIS) patients had a virus with predicted resistance/intermediate resistance to the PI/r initiated. Concordance between GISs on ascribed PI/r resistance levels was moderate: kappa values ranged from 0.01 to 1.00, with the lowest kappas seen for amprenavir. The median (interquartile range) baseline HIV-RNA was 4.4 (3.5-5.1) log10 and was reduced by 2.2 (2.1-2.3) log10 12 (9-13) weeks after baseline. GIS consistently showed greater HIV-RNA reductions as the ascribed level of sensitivity to the PI/r increased. Conversely, the number of other active drugs in the rest of the regimen, according to each GIS did not predict HIV-RNA reductions consistently.
: Despite large variations in how GIS classify HIV susceptibility to PI/r, all GIS predicted HIV-RNA reductions of a similar magnitude. The ascribed level of susceptibility to other drugs in the regimen did not predict HIV-RNA decline.
关于基因型解释系统（GISs）对利托那韦增强型蛋白酶抑制剂（PI/rs）的预后价值的信息有限。我们比较了四种GISs所确定的PI/r耐药水平，并研究了它们预测基于PI/r方案（基线）开始后HIV-RNA降低情况的能力。
将一项观察性队列研究（欧洲艾滋病临床数据库[EuroSIDA]）和三项随机试验（MaxCmin1、MaxCmin2和COLATE）中开始接受PI/r并进行基线耐药检测的病毒血症（HIV-RNA>500拷贝/ml）患者的数据合并。所调查的GISs为法国国家艾滋病研究机构（ANRS）、数据监测委员会（DMC）、鲁汶大学艾滋病研究与参考实验室（REGA）和斯坦福大学系统。通过删失回归分析确定与HIV-RNA变化相关的因素。
我们纳入了744例患者，其中67%有PI治疗史。基线时，12% - 28%（取决于GIS）的患者病毒对所启动的PI/r具有预测性耐药/中度耐药。GISs在所确定的PI/r耐药水平上的一致性为中等：kappa值范围为0.01至1.00，对于安普那韦，kappa值最低。基线时HIV-RNA的中位数（四分位间距）为4.4（3.5 - 5.1）log10，在基线后12（9 - 13）周降低了2.2（2.1 - 2.3）log10。随着所确定的对PI/r的敏感水平增加，GISs一致显示出更大的HIV-RNA降低。相反，根据每个GIS，方案中其他活性药物的数量并不能一致地预测HIV-RNA降低情况。
尽管GISs在对HIV对PI/r的易感性分类方式上存在很大差异，但所有GISs都预测了相似程度的HIV-RNA降低。方案中对其他药物的易感性水平并不能预测HIV-RNA下降。
