Lastere Stephane, Dalban Cecile, Collin Gilles, Descamps Diane, Girard Pierre-Marie, Clavel Francois, Costagliola Dominique, Brun-Vezinet Francoise
Laboratoire de Virologie, Hopital Bichat--Claude Bernard, Paris, France.
Antivir Ther. 2004 Apr;9(2):221-7.
We evaluated the impact of genetic changes within p6Gag gene on the virological response (VR, mean decrease in plasma viral load at week 12) to unboosted amprenavir (APV). Gag-protease fragments, including gag p2, p7, p1, p6 regions and whole protease (PR) were sequenced from baseline plasma specimens of 84 highly pre-treated but APV-naive patients included in the NARVAL (ANRS 088) trial. The correlation between baseline p6Gag polymorphism, PR mutations, baseline characteristics and VR to APV was analysed in univariate analysis. Insertions (P459Ins) within p6 protein, leading to partial or complete duplication of the PTAPP motif, were significantly associated with a decreased VR (P459Ins versus wild-type; -0.3 +/- 0.8 vs -1.1 +/- 1.2 log copies/ml, P=0.007) and were more frequent when the V82A/F/T/S PR mutation was present (P=0.020). In multivariate analysis, after adjustment on the predictive factors of the VR in the NARVAL trial and on the PR mutations linked with response, there was a strong trend to an association (P=0.058) between the presence of P459Ins and an altered VR. In conclusion, these results suggest that insertions in the p6 region of HIV-1 gag gene may affect the VR, in highly pre-treated patients receiving an unboosted APV-containing regimen.
我们评估了p6Gag基因内的基因变化对未增效安普那韦（APV）病毒学应答（VR，第12周时血浆病毒载量的平均下降）的影响。从纳入NARVAL（ANRS 088）试验的84例接受过高度预处理但未使用过APV的患者的基线血浆样本中，对包括gag p2、p7、p1、p6区域和整个蛋白酶（PR）的Gag-蛋白酶片段进行了测序。在单变量分析中，分析了基线p6Gag多态性、PR突变、基线特征与对APV的VR之间的相关性。p6蛋白内的插入（P459Ins）导致PTAPP基序部分或完全重复，与VR降低显著相关（P459Ins与野生型相比；-0.3±0.8对-1.1±1.2 log拷贝/ml，P = 0.007），并且当存在V82A/F/T/S PR突变时更频繁（P = 0.020）。在多变量分析中，在对NARVAL试验中VR的预测因素以及与应答相关的PR突变进行调整后，P459Ins的存在与VR改变之间存在强烈的关联趋势（P = 0.058）。总之，这些结果表明，在接受未增效含APV方案的高度预处理患者中，HIV-1 gag基因p6区域的插入可能会影响VR。
