HBx能反式激活HIV转录，是HBV合并感染加速艾滋病进展的重要原因。在HIV/HBV合并感染队列中，我们发现，艾滋病进展缓慢组的A1762T/G1764A双突变率较高；且前瞻性观察到，目标变异的新近感染者HIV载量较低。我们由此推测，位于HBx反式激活关键调控区的A1762T/G1764A变异后，其编码的变异蛋白丧失反式激活功能，使HIV复制能力下降，从而延缓艾滋病进展。为此，本项目将继续在艾滋病进展速度不同人群中，调查目标位点突变的分子流行差异；临床队列观察，目标变异对新近感染者HIV调定点、初始CD4+T淋巴细胞数、HIV分离株复制能力及后续HIV储存库的影响；进一步应用细胞共培养技术，验证目标突变株对HIV体外复制能力的影响；最后利用不同HIV毒株感染TZMBL细胞体系，验证目标变异蛋白对HIV体外复制的抑制效应。本项目可为研究艾滋病新型干预手段和探索基因治疗策略提供新思路。

HIV transcription can be trans-activated by HBx, which is an important reason for HBV co-infection to accelerate the disease progression after HIV infection. In HIV/HBV co-infection cohort, we found that HBx with A1762T/G1764A double mutation was more common in slow AIDS progression population. In further prospectively observation, we found that the level of HIV viral load in newly infected patients with A1762T/G1764A double mutation was lower compared to those patients with HBx wild type infection. We followed this clue and speculated that the trans-activation function of HBx could disappear after A1762T/G1764A mutation, which could lead to lower level of HIV replication and further delay AIDS progression. Therefore, on the basis of our preliminary work, this study will continue to investigate the epidemic of A1762T/G1764A double mutation in people with different rates of AIDS progression. Then in HIV newly infected clinical cohort, the effects of A1762T/G1764A mutation on HIV set point viral load, initial CD4+T lymphocyte count, the replication capacity of HIV isolates and magnitude of the latent HIV reservoir will be prospectively observed. Further, the cells co-culture model will be applied to verify the effect of A1762T/G1764A double mutation on HIV replication capacity in vitro. Finally, the system of TZMBL cells infected by different HIV strains will be used to explore the inhibitory effect of HBx-A1762T/G1764A mutation protein on HIV replication in vitro. This study could provide new ideas for researchers on new-style intervention measures and gene therapy strategy for AIDS.