“免疫代谢”对揭示疾病转归机制及干预具有重要作用，但是否影响HIV感染疾病快速进展尚不可知。我们首次发现，血浆脂肪酸代谢物可在HIV感染早期有效预测疾病快速进展，进展者CD8+T细胞脂肪酸氧化关键酶表达升高，提示脂肪酸代谢“重塑”（Reprogramming），脂肪酸氧化增强。我们推测：早期大量抗原刺激等导致低糖及细胞因子微环境改变，促使快速进展者效应T细胞代谢向脂肪酸氧化重塑，不能有效支撑其功能发挥，并通过促进调节性T细胞分化、诱导PPARγ表达等削弱T细胞效应功能，导致疾病进展。为证实以上假设，本研究拟明确：1）HIV快速进展者T细胞脂肪酸代谢重塑情况；2）脂肪酸代谢重塑对T细胞功能的影响及机制；3）导致快速进展者T细胞脂肪酸代谢重塑的上游因素；4）干预脂肪酸代谢重塑对快速进展者T细胞免疫损伤的恢复，最终明确脂肪酸代谢重塑对HIV感染快速进展的影响，为免疫治疗等提供创新靶点。

Immunemetabolism plays an important role in revealing the pathogenic mechanism and providing intervention strategy of immune related diseases, but whether it contributes to the rapid progression of HIV infection is unknown. We found for the first time, plasma fatty acid metabolites in the early stage of HIV infection effectively predict disease progression. The expression of fatty acid oxidation enzyme in CD8+T cells from progressors is significantly increased compared with non-progressors. These data suggest that there is a fatty acid metabolism “reprogramming” in HIV infected rapid progressors. We postulated that the enhancement of fatty acid oxidative may weaken the immune response through the insufficient metabolic support of T cell function and the induction of regulatory T cells and PPARγ expression. To prove the hypothesis, this study intends to clarify: 1) The fatty acid metabolism reprogramming in the T cell of rapid progressors; 2) The effect and mechanisms of fatty acid metabolism reprogramming on T cell immune responses; 3) The factors driving T cell fatty acid reprogramming in rapid progressors; 4) The restore of T cell immune responses of rapid progressors by the intervention of fatty acid reprogramming. Our data will clarify the effect and mechanisms of fatty acid metabolism reprogramming on HIV disease rapid progression and provide potential targets for immune therapy.