云南省是艾滋病流行重灾区，马尔尼菲青霉菌病（PSM）是本地区艾滋病患者的重要死亡原因，临床研究提示艾滋病合并PSM患者病毒载量显著上升，CD4+T淋巴细胞数量急剧下降，抗真菌治疗基础上尽早联合抗病毒治疗可显著降低患者病死率。我们前期研究发现马尔尼菲青霉菌（PM）可通过DC促进HIV的感染和复制，且经PM刺激成熟的DC上清可激活HIV潜伏感染细胞系。提示HIV潜伏库的激活可能与艾滋病合并PSM患者病情急剧恶化相关。本项目拟采用体内和体外两个实验体系进行印证研究：于治疗前及治疗后0.5、1、3、6月进行免疫细胞数量及功能，病毒载量和潜伏病毒库变化，临床指标及预后，细胞因子动态研究，以阐明马尔尼菲青霉菌激活HIV潜伏感染相关的免疫学机制；并通过体外实验探索PM激活HIV潜伏感染相关的分子机制。从而阐明PM感染导致艾滋病患者病情急剧恶化的机制，为优化艾滋病合并PSM的治疗提供理论依据。

Yunnan province is the AIDS epidemic disaster area in China,and Penicilliosis maneffei (PSM) is an important cause of death among AIDS patients. Clinical studies show that HIV viral load raise obviously and the numbers of CD4+T lymphocytes decline dramaticly among AIDS patients with PSM.Antifungal therapy combined with early HARRT treatment could significantly reduce the mortality.Our previous research showed that Penicillium maneffei(PM) could promote HIV infection and replication by DC, and the supernatant of mature DC cells stimulated by PSM could activate HIV latency cell line.Our results suggest the activation of HIV latency Library may be related to therapidly worsened condition among AIDS patients with PSM. This project intends to verify the mechanism by in vivo and in vitro experimental systems.During treatment time 0,0.5,1,3,6 months,we will detect dynamicly immune cells amounts and function, HIV viral load and HIV latency Library, clinical indicators and prognosis,cytokines level.The results could explain the immunological mechanism of HIV latency activated by PM. And molecular mechanisms of HIV latency activated by PM will be illustrated in vitro study. The study should clarify the rapid deterioration mechanism of AIDS patients with PSM,.and provide the theoretical basis for optimization treatment.