Laboratoire de Virologie, AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Univ Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
AIDS. 2013 Jan 2;27(1):69-80. doi: 10.1097/QAD.0b013e32835a10d8.
This study investigated the impact on virological outcome of the gag cleavage sites and the protease-coding region mutations in protease inhibitor-naive and protease inhibitor-experienced patients infected with HIV-2 receiving lopinavir (LPV) containing regimen.
Baseline gag and protease-coding region were sequenced in 46 HIV-2 group A-infected patients receiving lopinavir. Virological response was defined as plasma viral load less than 100 copies/ml at month 3. Associations between virological response and frequencies of mutations in gag [matrix/capsid (CA), CA/p2, p2/nucleocapsid (NC), NC/p1, p1/p6] and gag-pol (NC/p6) cleavage site and protease-coding region, with respect to the HIV-2ROD strain, were tested using Fisher's exact test.
Virological response occurred in 14 of 17 (82%) protease inhibitor-naive and 17 of 29 (59%) protease inhibitor-experienced patients. Virological failure was associated with higher baseline viral load (median: 6765 versus 1098 copies/ml, P = 0.02). More protease-coding region mutations were observed in protease inhibitor-experienced compared with protease inhibitor-naive patients (median: 8 versus 5, P = 0.003). In protease inhibitor-naive patients, T435A (NC/p6), V447M (p1/p6), and Y14H (protease-coding region) were associated with virological failure (P = 0.011, P = 0.033, P = 0.022, respectively). T435A and V447M were associated with Y14H (P = 0.018, P = 0.039, respectively). In protease inhibitor-experienced patients, D427E (NC/p1) was associated with virological response (P = 0.014). A430V (NC/p1) and I82F (protease-coding region) were associated with virological failure (P = 0.046, P = 0.050, respectively). Mutations at position 430 were associated with a higher number of mutations in protease-coding region (median: 10 versus 7, P = 0.008).
We have demonstrated, for the first time, an association between gag, gag-pol cleavage site and protease-coding region mutations, with distinct profiles between protease inhibitor-naive and protease inhibitor-experienced patients. These mutations might impact the virological outcome of HIV-2-infected patients receiving LPV-containing regimen.
本研究旨在探讨 HIV-2 感染者在接受洛匹那韦（LPV）为基础的治疗方案时 gag 裂解位点和蛋白酶编码区突变对病毒学结果的影响。
对 46 例感染 HIV-2 组 A 的患者进行基线 gag 和蛋白酶编码区测序。病毒学反应定义为第 3 个月时血浆病毒载量小于 100 拷贝/ml。使用 Fisher 确切检验检测 gag [基质/衣壳 (CA)、CA/p2、p2/核衣壳 (NC)、NC/p1、p1/p6]和 gag-pol (NC/p6)裂解位点以及蛋白酶编码区中突变与 HIV-2ROD 株的频率与病毒学反应之间的关系。
17 例初治（82%）和 29 例经治（59%）患者中，14 例和 17 例患者发生病毒学失败。病毒学失败与较高的基线病毒载量（中位数：6765 与 1098 拷贝/ml，P=0.02）相关。与初治组相比，经治组观察到更多的蛋白酶编码区突变（中位数：8 与 5，P=0.003）。在初治组中，T435A（NC/p6）、V447M（p1/p6）和 Y14H（蛋白酶编码区）与病毒学失败相关（P=0.011、P=0.033、P=0.022，分别）。T435A 和 V447M 与 Y14H 相关（P=0.018、P=0.039，分别）。在经治组中，D427E（NC/p1）与病毒学反应相关（P=0.014）。A430V（NC/p1）和 I82F（蛋白酶编码区）与病毒学失败相关（P=0.046、P=0.050，分别）。位置 430 的突变与蛋白酶编码区中更多的突变相关（中位数：10 与 7，P=0.008）。
我们首次证明了 gag、gag-pol 裂解位点和蛋白酶编码区突变之间的相关性，在初治和经治患者中具有不同的特征。这些突变可能影响接受 LPV 为基础的治疗方案的 HIV-2 感染者的病毒学结果。
