Cozzi-Lepri Alessandro, Phillips Andrew N, Ruiz Lidia, Clotet Bonaventura, Loveday Clive, Kjaer Jesper, Mens Helene, Clumeck Nathan, Viksna Ludmila, Antunes Francisco, Machala Ladislav, Lundgren Jens D
Royal Free and University College Medical School, London, UK.
AIDS. 2007 Mar 30;21(6):721-32. doi: 10.1097/QAD.0b013e3280141fdf.
To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting.
The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml.
Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0).
At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2.
In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.
评估接受病毒学治疗失败方案的患者中耐药性累积的程度及其在临床环境中的决定因素。
该研究聚焦于110例欧洲艾滋病临床数据库（EuroSIDA）患者，他们使用不变的治疗方案，在病毒载量>400拷贝/毫升时的两个时间点（t0和t1）进行了两次基因分型检测。
使用基因型易感性评分（GSS）测量t0和t1之间的耐药性累积，GSS通过计算截至2006年1月1日所有已获许可的抗逆转录病毒药物中的活性药物总数（根据Rega系统v6.4.1）获得。患者根据t0时失败方案中的活性药物数量进行分组（GSS_f-t0）。
在t0时，患者接受失败的联合抗逆转录病毒治疗（cART）的中位时间为11个月（范围为6 - 50个月）。即使是对失败方案有广泛耐药性的患者仍从治疗中获益。估计国际艾滋病协会突变总体每6个月增加1.96（标准差2.23），活性药物平均减少1.25（标准差1.81）。与GSS_f-t0 = 0的患者相比，GSS_f-t0为0.5 - 1.5的患者活性药物减少数量为-1.08 [95%置信区间（CI），-2.13至-0.03；P = 0.04]，GSS_f-t0≥2的患者为-1.24（95% CI，-2.44至-0.04；P = 0.04）。
在接受相同病毒学治疗失败的cART方案中位时间为6个月的患者中，耐药性突变有相当程度的累积，特别是对失败方案初始耐药水平较低的患者。在等待新的抑制性治疗可用期间，对维持治疗策略进行随机比较是必要的。
