Role of HIV Gag mutations in acquisition of resistance to protease inhibitors.

在体外筛选的氨丙那韦(APV)耐药病毒中，我们鉴定了Gag区的6个氨基酸替换。携带Gag突变的感染性重组HIV-1克隆比野生型HIV-1更快地产生对APV的耐药性，但它推迟了对另一种PI奈非那韦(Nelfinavir，NFV)的耐药性的获得，表明同时包括APV和NFV的抗逆转录病毒方案可能具有良好的抗病毒效果。目前的数据表明，与PI抗性相关的某些GAG突变的预先存在可以加速对PI的耐药性的出现，并延迟HIV对其他PI的耐药性的获得。这些发现对PI-包括方案治疗HIV-1感染具有临床意义。

We have identified six amino acid substitutions in the Gag region in in vitro selected amprenavir (APV)-resistant viruses. An infectious recombinant HIV-1 clone carrying the Gag mutations developed APV resistance more quickly than wild-type HIV-1, however it delayed the acquisition of resistance against nelfinavir (NFV) which is another PI, suggesting that antiretroviral regimens including both APV and NFV may bring about favorable antiviral efficacy. The present data suggests that the preexistence of certain Gag mutations related to PI resistance can accelerate the emergence of resistance to the PI and delay the acquisition of HIV resistance to other PIs. These findings should have clinical relevance in the therapy of HIV-1 infection with PI-including regimens.