Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC Université Paris 06, INSERM U943, Paris, France.
J Antimicrob Chemother. 2011 Jul;66(7):1481-3. doi: 10.1093/jac/dkr152. Epub 2011 Apr 7.
To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients.
Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed.
The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient).
T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. The impact of raltegravir-mediated changes such as these on the virological response to S/GSK1349572 should be studied further.
比较先前在体外选择的整合酶突变（T124A、T124A/S153F、S153Y、T124A/S153Y 和 L101I/T124A/S153Y）在对 S/GSK1349572 具有耐药性的 HIV-1 亚型 B 整合酶抑制剂（INI）初治和拉替拉韦治疗患者中的频率。
分析了 650 例 INI 初治患者和 84 例拉替拉韦治疗患者的整合酶序列。
单独的 T124A 突变和 T124A/L101I 组合在拉替拉韦失败患者中比 INI 初治患者更为常见（分别为 39.3%和 24.5%，P = 0.005；分别为 20.2%和 10.0%，P = 0.008）。除了单独的 S153F（仅在 1 例 INI 初治患者中检测到）外，未在任何整合酶序列中检测到 S153Y/F 突变。
在拉替拉韦治疗患者中更为常见的 T124A 和 T124A/L101I 可能对拉替拉韦的反应有一定影响，其存在可能在选择其他对 S/GSK1349572 耐药的突变中起作用。应该进一步研究这些由拉替拉韦介导的变化对 S/GSK1349572 的病毒学反应的影响。
