摘要
目的针对长期接受抗逆转录病毒治疗(antiretroviral therapy,ART)的免疫无应答者(immunological non-responders,INRs)和免疫应答者(immunological responders,IRs),研究INRs和IRs的HIV储存库和α4β7细胞的动态变化及其相关性。方法入组接受ART时长5年的慢性HIV感染者26例,根据免疫重建分为INRs(CD4^(+)T细胞计数≤350个/μl,n=9)和IRs(CD4^(+)T细胞计数≥500个/μl,n=17)。采用流式细胞术检测基线、ART 1、3、5年时两组的α4β7细胞占比和数量,实时荧光定量PCR检测同期HIV DNA和细胞相关HIV RNA水平。比较两组在基线、ART 1、3、5年时HIV病毒衰减、α4β7细胞变化及其与T细胞之间的相关性。结果5年ART期间,与IRs相比,INRs的HIV储存库水平较高,但衰减趋势不慢,同时α4β7细胞计数较低且增长趋势慢(P均<0.05)。α4β7细胞计数与同期CD4^(+)T细胞计数始终成正相关(ART 1年r=0.887,ART 3年r=0.878,ART 5年r=0.887,P均<0.001),与同期CD38^(+)HLA-DR^(+)CD4^(+)T细胞呈负相关(ART 1年r=-0.619,P=0.001)和CD38^(+)HLA-DR^(+)CD8^(+)T细胞呈负相关(ART 1年r=-0.517,ART 5年r=-0.532,P均<0.01),与同期PD-1^(+)CD4^(+)T细胞呈负相关(ART 1年r=-0.476,ART 5年r=-0.390,P均<0.05)。结论长期ART期间,与IRs相比,INRs维持较高的HIV储存库水平及较低的α4β7细胞计数,且α4β7细胞减少可能与疾病进展有关。
Objective To investigate immunological non-responders(INRs)and immunological responders(IRs)during long-term antiretroviral therapy(ART),and study the dynamics of HIV reservoir andα4β7 cells in INRs and IRs and their correlation.Methods Twenty-six patients with chronic HIV infection who received ART for 5 years were included.They were divided into INRs(CD4^(+)T cell counts≤350 cells/μl,n=9)and IRs(CD4^(+)T cell counts≥500 cells/μl,n=17)based on immune reconstitution outcomes.The percentages and numbers ofα4β7 cells in both groups at baseline,ART 1,3,and 5 years were detected by flow cytometry,and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods.HIV viral decay,α4β7 cells dynamics,and their correlations with T cells were compared at baseline,ART 1,3 and 5 years between the two groups.Results Over 5 years of ART,INRs exhibited higher HIV reservoir levels compared to IRs,but the decline trend was not slow.The counts ofα4β7 cell were lower and the growth trend was slow in INRs(P<0.05).α4β7 cell counts were strongly positively correlated with CD4^(+)T cell counts at all timepoints(Year 1:r=0.887;Year 3:r=0.878;Year 5:r=0.887;P all<0.001),while showing significantly negative correlations with activated CD38^(+)HLA-DR^(+)CD4^(+)T cells(Year 1:r=-0.619,P=0.001),CD38^(+)HLA-DR^(+)CD8^(+)T cells(Year 1:r=-0.517;Year 5:r=-0.532;P all<0.01),and PD-1^(+)CD4^(+)T cells(Year 1:r=-0.476,Year 5:r=-0.390,P all<0.05).Conclusions During long-term ART,INRs maintained higher HIV reservoir and lowerα4β7 cell counts compared with IRs,and decreasedα4β7 cells may be associated with disease progression.
作者
高玲羽
李雪霁
焦艳梅
屈蒙蒙
徐峥
史继静
杨宝鹏
张禄雪
Gao Lingyu;Li Xueji;Jiao Yanmei;Qu Mengmeng;Xu Zheng;Shi Jijing;Yang Baopeng;Zhang Luxue(Key Medical Laboratory of Stem Cell Transformation and Application,the First People′s Hospital of Zhengzhou,Zhengzhou 450000,China;Dermatology and STD Department,Beijing Huairou Hospital,Beijing 101400,China;Department of Infectious Diseases,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Infectious Disease Department,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)
出处
《中华微生物学和免疫学杂志》
北大核心
2025年第4期285-292,共8页
Chinese Journal of Microbiology and Immunology
基金
国家自然科学基金(82302511)。
作者简介
通信作者:张禄雪,Email:zlx2512@163.com;通信作者:杨宝鹏,Email:g8_1980530@126.com。
