Yerly Sabine, Fagard Catherine, Günthard Huldrych F, Hirschel Bernard, Perrin Luc
Laboratory of Virology, Geneva University Hospital, Switzerland.
Antivir Ther. 2003 Oct;8(5):411-5.
We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss-Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40.
Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound > 500 copies/ml off treatment and preceding failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml after week 40.
Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all but two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007).
The M184V/I mutation is frequently selected during repeated treatment interruptions.
在瑞士 - 西班牙间歇性治疗试验（SSITT）中，我们评估了治疗中断是否会诱导与耐药性相关的突变选择。患者此前接受高效抗逆转录病毒治疗（HAART）且未出现过治疗失败，病毒血症检测不到至少达6个月。他们的HAART中断2周，然后重新开始8周。经过4个这样的周期后，在第40周彻底中断治疗。
对87/97名瑞士患者进行了基因型耐药性检测：对于在第40周前治疗失败的患者，在首次病毒反弹>500拷贝/毫升且停止治疗时，以及重新治疗8周后未能达到RNA<50拷贝/毫升之前进行检测；对于无病毒学失败的患者，在第40周后首次HIV - 1 RNA>1000拷贝/毫升的样本上进行检测。
在最初40周内出现病毒学失败的25名患者中有9名（36%）检测到与耐药性相关的突变，在第40周后59名患者中有6名（10%）检测到。总体而言，17%的患者检测到耐药性突变，除两名患者外均为184V/I突变。在接受拉米夫定的74名患者中，13/74（17.6%）名患者检测到M184V/I突变。除两名患者外，之前的样本中均检测到184位的野生型密码子。M184V/I突变患者病毒学失败的相对风险比未检测到突变的患者高2.55倍（P = 0.007）。
在反复的治疗中断期间，M184V/I突变经常被选择出来。
