不同抗病毒治疗方案对HIV病毒库的影响  

Effects of Different Antiviral Therapy Regimens on the HIV Virus Reservoir

作　　者：陈思源[1] 刘奉凤 黄成瑜 白艳[1] 李梅[1] CHEN Siyuan;LIU Fengfeng;HUANG Chengyu;BAI Yan;LI Mei(Department of Infectious Diseases,Chongqing Public Health Medical Center,Chongqing 400036,China)

机构地区：[1]重庆市公共卫生医疗救治中心感染科,重庆400036

出　　处：《中国卫生标准管理》2023年第18期36-40,共5页China Health Standard Management

基　　金：重庆市科卫联合医学科研项目(2020FYYX170)。

摘　　要：目的随着抗逆转录病毒疗法(antiretroviral therapy,ART)的进步,使艾滋病(acquired immune deficiency syndrome,AIDS)从一种致死性疾病转化为可治疗的慢性感染性疾病。通过前瞻性队列研究,掌握整合酶抑制剂(integrase inhibitors,INSTI)时代不同ART方案降低人类免疫缺陷病毒1型(human immunodeficiency virus-1,HIV-1)DNA速率的特征和结局,探索最佳治疗模型。方法选取2020年9月—2022年8月重庆市公共卫生医疗救治中心招募的HIV感染者,采用前瞻性队列研究方法,实时PCR对外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中的总HIV-1 DNA进行定量,这些PBMC采集自744例初治及经治感染者,分为四组同时进行临床观察:第一组初治,第3种药物为非核苷类反转录酶抑制剂(non-nucleoside reverse transcriptase inhibitors,NNRTI)。第二组初治,第3种药物为INSTI。第三组经治,继续原方案使用NNRTI。第四组经治,由NNRTI转换成INSTI。在治疗前(0周)及治疗后每3个月(3、6、9、12、15、18、21、24个月),检测病毒载量(HIV-1 RNA)、CD4^(+)T淋巴细胞(CD4^(+)T lymphocyte,CD4^(+))、CD4^(+)/CD8^(+)T淋巴细胞(CD8^(+)T lymphocyte,CD8^(+))比值及HIV-1 DNA定量水平。观察不同治疗方案HIV-1 DNA下降速率及HIV-1 DNA水平是否有差异。结果初治HIV感染者只要采用规范的抗病毒治疗方案,无论是INSTI联合治疗方案或NNRTI联合治疗方案,HIV-1 DNA均获得有效降低,INSTI治疗组的HIV-1 DNA减少较NNRTI治疗组更明显。经治HIV感染者,不管继续原方案或转换成INSTI,HIV-1 DNA量未发现差异。结论HIV-1 DNA水平是初治患者治疗方案评估的新指标;最新一代药物,如INSTI可能是治疗HIV感染的最佳选择。Objective With the advancement of antiretroviral therapy(ART),acquired immune deficiency syndrome(AIDS)has been transformed from a fatal disease to a treatable chronic infectious disease.Through prospective cohort studies,we aim to understand the characteristics and outcomes of different ART regimens in reducing human immunodeficiency virus-1(HIV-1)DNA levels in the era of integrase inhibitors(INSTI),and to explore the best treatment model.Methods Using a prospective cohort study method and real-time PCR to quantify total HIV-1 DNA in peripheral blood mononuclear cells(PBMC)from HIV-infected individuals recruited from the Chongqing Public Health Medical Center from September 2020 to June 2021.These PBMC were collected from 744 treatment-naive and treatment-experienced individuals,divided into four groups for simultaneous clinical observation.Group 1,treatment-naive,third drug non-nucleoside reverse transcriptase inhibitors(NNRTI).Group 2,treatment-naive,third drug INSTI.Group 3,treatment-experienced,continued original regimen with NNRTI.Group 4,treatment-experienced,switched from NNRTI to INSTI.Viral load,CD4^(+)T lymphocytes(CD4^(+)),CD4^(+)/CD8^(+)T lymphocyte(CD8^(+))ratio and HIV-1 DNA levels were measured before treatment(week 0)and every 3 months after treatment(3,6,9,12,15,18,21,24 months).The rate of decline in HIV-1 DNA levels and differences in HIV-1 DNA levels between different treatment regimens were observed.Results HIV-1 DNA was effectively reduced in patients who had just started treatment as long as they adopted standard antiviral therapy,whether INSTI combination therapy or NNRTI combination therapy,and the reduction of HIV-1 DNA in INSTI treatment group was more significant than that in NNRTI treatment group.In treatment-experienced HIV-infected individuals,no difference correlation was found between HIV-1 DNA levels and continuation of the original regimen or switching to INSTI.Conclusion The level of HIV-1 DNA is a predictive factor for treatment-naive patients.The latest generation of drugs s

关 键 词：HIV-1 DNA HIV-1 RNA CD4^(+)细胞 抗逆转录病毒疗法 整合酶抑制剂 病毒库 

分 类 号：R512[医药卫生—内科学]